Patent Publication Number: US-2022211835-A1

Title: Replication Deficient Adenoviral Vectors for HIV Vaccine Applications

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     The present application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 62/835,108 filed Apr. 17, 2019, which is incorporated herein by reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     HIV infection is prevalent worldwide, spurring a quest to develop efficient vaccines to treat or prevent HIV infection. The situation is also true in China and Asia. Vaccination is widely recognized as the most effective method of preventing or ameliorating morbidity from infectious diseases. Viral vector vaccines, such as those based on adenoviral vectors, may be used against various infectious and malignant diseases (Small and Ertl, Curr Opin Virol. 2011, October 1; 1(4): 241-245). 
     There is a need in the art for methods of producing more efficient adenovirus vector vaccine systems for treating or preventing HIV infection. The need is especially pressing in China and other countries in Asia. The present invention fulfills this need. 
     SUMMARY 
     Provided is a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag;
         wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C; and   wherein Gag is from a Chinese HIV clade B.       

     In some embodiments, the expression cassette is in the early gene E1 genomic region. In some embodiments, the expression cassette comprises a chimeric intron and/or CMV enhancer. In some embodiments, the early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. In further embodiments, the entire early gene E3 genomic region is deleted. 
     In some embodiments, the promoter is a constitutive promoter. In further embodiments, the promoter is a cytomegalovirus immediate early promoter (CMV). 
     In some embodiments, the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. 
     Provided is a protein expression system comprising the the composition of any one of the previous embodiments, wherein the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. 
     Also provided is a protein expression system comprising the composition of any one of the preceding embodiments, wherein the heterologous protein encoded by the expression cassette comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5. 
     Provided is a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a constitutive promoter operably linked to a sequence encoding a heterologous protein, wherein the expression cassette is in the early gene E1 genomic region, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag;
         wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C; and   wherein Gag is from a Chinese HIV clade B.       

     In some embodiments, the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. 
     Provided is a protein expression system comprising the composition of any one of the preceding embodiments, wherein the heterologous protein encoded by the expression cassette comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5. 
     Provided is a method of eliciting an immune response in a mammal against a heterologous protein, the method comprising administering to the mammal a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag;
         wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C; and   wherein Gag is from a Chinese HIV clade B.       

     In some embodiments, the expression cassette is in the early gene E1 region. In some embodiments, the expression cassette comprises a chimeric intron and/or CMV enhancer. 
     In some embodiments, an early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. In further embodiments, the entire early gene E3 genomic region is deleted. 
     In some embodiments, the promoter is a constitutive promoter. In further embodiments, the promoter is a cytomegalovirus immediate early promoter (CMV). 
     In some embodiments, the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. 
     Provided is a method of treating and/or preventing HIV in a mammal, the method comprising administering a therapeutically effective amount of a composition encoded by a nucleic acid sequence comprising SEQ ID NOs: 6 or 7. 
     Also provided is a method of vaccinating a mammal against HIV infection, the method comprising administering to the mammal a therapeutically effective amount of the the composition of any one of the previous embodiments, wherein administration of the composition elicits an immune response in the mammal. In some embodiments, the composition is administered prophylactically to the mammal. In further embodiments, the composition is administered therapeutically to the mammal. In yet further embodiments, the composition is administered in combination with an adjuvant. 
     Provided is a method of generating an effector and memory T cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of any one of the previous embodiments to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the composition of any one of the previous embodiments at a second, subsequent time period, wherein T memory cells directed against the heterologous protein are reactivated in the mammal. In some embodiments, the composition administered first in (a) and second in (b) comprises a same or a different HIV heterologous protein selected from the group consisting of gp140 and Gag. In further embodiments, the composition administered first in (a) and second in (b) is a same or a different serotype selected from the group consisting of AdC6 and AdC7. In yet further embodiments, the composition administered first in (a) and second in (b) is of a same or a different HIV Clade. 
     In some embodiments, the method further comprises the step of administering an immunogen to the mammal. In some embodiments, the immunogen comprises a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag; wherein gp140 is from a Chinese HIV Clade selected from the group consisting of B, AE, BC and C; and wherein Gag is from a Chinese HIV clade B, wherein a B cell immune response is further augmented. 
     Provided is a method of generating an adaptive B cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of any one of the previous embodiments to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the composition of any one of the previous embodiments at a second, subsequent time period, wherein B memory cells directed against the heterologous protein are reactivated in the mammal. In some embodiments, the composition administered first in (a) and second in (b) comprises a same or a different HIV heterologous protein selected from the group consisting of gp140 and Gag. In further embodiments, the composition administered first in (a) and second in (b) has a same or a different serotype selected from the group consisting of AdC6 and AdC7. In yet further embodiments, the composition administered first in (a) and second in (b) is of a same or a different HIV Clade. 
     In some embodiments, the method further comprises the step of administering an immunogen to the mammal. In some embodiments, the immunogen comprises a heterologous protein, wherein the heterologous protein is at least one HIV env protein selected from any Clade from any source, wherein the B cell immune response is further augmented. 
     In some embodiments, the mammal is a human. 
     Any and all features of the aspects or embodiments may be combined to achieve new embodiments. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       For the purpose of illustrating the invention, there are depicted in the drawings certain embodiments of the invention. However, the invention is not limited to the precise arrangements and instrumentalities of the embodiments depicted in the drawings. 
         FIG. 1A  is a series of graphs illustrating percentage of CD8 + CD44 +  cells over all CD8 + CD44 +  cells from blood releasing cytokines in response to gag peptide. Background responses without the gag peptide were subtracted. Lines show mean responses ±SD. Line with stars above indicates a significant difference (p&lt;0.01).  FIG. 1B  is series of graphs illustrating percentage of CD8 + CD44 +  cells over all CD8 + CD44 +  cells from pooled blood of mice immunized 14 days earlier with 10 11  virus particles (vp) of the AdC6gag or AdC7gag vectors producing cytokines in response to a peptide carrying the immunodominant epitope of gag. Background responses without gag peptide were subtracted. 
         FIG. 2  is series of graphs illustrating percentage of specific CD8 + CD44 +  cells over all CD8 + CD44 +  cells tested from spleens of individual mice 18 days after their immunization with 10 11  virus particles (vp) of the AdC6gag or AdC7gag vectors producing the indicated cytokines in response to gag peptide. The sum reflects the total response calculated based on Boolean gating. Background responses without gag peptide were subtracted. 
         FIGS. 3A-3B  are a series of graphs showing T cell responses tested from pooled blood 14 days after immunization with 10 10  or 10 9  vp of the AdC6gag vector. The graph layout mirrors that of  FIG. 1 .  FIG. 3A  shows CD8 +  T cell responses,  FIG. 3B  shows CD4 +  T cell responses. 
         FIG. 4  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the indicated vectors on plates coated with gp140 protein of Clade C, AE or BC. Circles—mice immunized with AdC6 vectors. Squares—mice immunized with AdC7 vectors. Values obtained with sera from naïve mice were subtracted. Lines show medians. nt—not tested. 
         FIG. 5  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the indicated vectors followed by a boost with 10 9  vp of the heterologous vectors expressing the same insert on plates coated with gp140 protein of Clade C, AE or BC. Circles—mice immunized with AdC6 and the AdC7 vectors. Squares—mice immunized with AdC7 and then boosted with AdC6 vectors. Values obtained with sera from naïve mice were subtracted. Lines show medians. nt—not tested. 
         FIG. 6  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the AdC6 vectors followed by a boost with 10 9  vp of the AdC7 vectors expressing the same insert and then a second boost with a Clade C protein in alum on plates coated with gp140 protein of Clade C, AE or BC. Values obtained with sera from naïve mice were subtracted. Lines show medians. 
         FIG. 7  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the AdC6 vectors (circles) and after a boost with 10 9  vp of the AdC7 vectors (squares) expressing the same insert on plates coated with gp140 protein of Clade C, AE or BC. Values obtained with sera from naïve mice were subtracted. Lines show medians. These data are similar to those in  FIGS. 4 and 5  but the assays for the 2 time points were conducted simultaneously to allow for a direct comparison. 
         FIG. 8  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the AdC7 vectors (circles) and after a boost with 10 9  vp of the AdC6 vectors (squares) expressing the same insert on plates coated with gp140 protein of Clade C, AE or BC. Values obtained with sera from naïve mice were subtracted. Lines show medians. These data are similar to those in  FIGS. 4 and 5  but the assays for the 2 time points were conducted simultaneously to allow for a direct comparison. 
         FIG. 9  shows ELISA results obtained with serum samples harvested and tested after priming with 10 11  vp of the AdC6 vectors followed by boosting with 10 9  vp of the AdC7 vectors (squares) expressing the same insert and then a second boost with a Clade C protein in alum on plates coated with gp140 protein of Clade C, AE or BC. Values obtained with sera from naïve mice were subtracted. Lines show medians. Lines with stars above indicate significant differences by 2-way Anova. These data are similar to those in  FIGS. 5 and 6  but the assays for the 2 time points were conducted simultaneously to allow for a direct comparison. 
         FIG. 10  shows a combination of the data shown in  FIGS. 6-8 . 
         FIG. 11  shows adsorbance values of the different sera from individual mice group correlated according to the insert used for immunization against the three different Clades (C, AE and BC) used for testing. The Figure shows r-values. Significant values are indicated by stars above the bars. 
         FIG. 12  shows frequencies of gag-specific CD8+ T cells 2 weeks after priming AdC6gag or AdC7gag vectors tested with pooled blood (left) and after a boost with the heterologous vector tested 2 weeks later using PBMCs from individual mice. The experiment was controlled using PBMCs from naïve mice. Results show the sum of all cytokines (IFN-gamma, IL-2, granzyme B and TNF-alpha) calculated upon Boolean gating. 
         FIG. 13  shows frequencies of gag-specific CD8+ T cells 2 weeks after priming with the AdC6gag (left) and 4 weeks after a boost with the AdC7gag vector. Results show the sum of all cytokine (IFN-gamma, IL-2, granzyme B and TNF-alpha) calculated upon Boolean gating. 
         FIG. 14  shows antibody responses as adsorbance against clade C env after priming of BALB/c mice with a mixture of the different AdC6gp140 vectors given each at 10 9  or 10 10  vp followed 6 weeks later by a boost with the AdC7gp140 vectors given at the same doses followed 6 weeks later by a Clade C env protein boost. The experiment was controlled by sera from naïve BALB/c mice. 
         FIG. 15  shows antibody responses as adsorbance against clade C, AE and BC env after priming of ICR mice with a mixture of the different AdC6gp140 or AdC7gp140 vectors given each at 10 10  vp followed 8 weeks later by a boost with the heterologous vectors vector given at the same doses. The experiment was controlled by sera from naïve ICR mice. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention relates to compositions and methods for generating a chimpanzee-derived adenovirus vector comprising a nucleic acid sequence comprising a deletion in some of the adenovirus early genes (i.e. wherein an early gene E1 region is deleted, and wherein in some embodiments ORF3, ORF4, ORF5, ORF6, and ORF7 from early gene E3 or the entire E3 gene are also deleted) and a promoter sequence linked to a sequence encoding a heterologous protein comprising, in certain embodiments, an HIV protein selected from the group consisting of gp140 and Gag; wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C; and wherein Gag is from a Chinese HIV clade B. Additionally, the current invention includes compositions and methods of treating of and/or preventing or immunizing against, a specific disease or disorder, and methods of inducing an effector and memory T and B cell immune response in a mammal administered the chimpanzee-derived adenovirus vector the invention. 
     Definitions 
     Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein may be used in the practice for testing of the present invention, the preferred materials and methods are described herein. In describing and claiming the present invention, the following terminology will be used. 
     It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. 
     As used herein, the articles “a” and “an” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. 
     The term “antibody” or “Ab” as used herein, refers to a protein, or polypeptide sequence derived from an immunoglobulin molecule, which specifically binds to a specific epitope on an antigen. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. The antibodies useful in the present invention may exist in a variety of forms including, for example, polyclonal antibodies, monoclonal antibodies, intracellular antibodies (“intrabodies”), Fv, Fab and F(ab) 2 , as well as single chain antibodies (scFv) and humanized antibodies (Harlow et al., 1998, Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y.; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426). An antibody may be derived from natural sources or from recombinant sources. Antibodies are typically tetramers of immunoglobulin molecules. 
     The term “ameliorating” or “treating” means that the clinical signs and/or the symptoms associated with a disease are lessened as a result of the actions performed. The signs or symptoms to be monitored will be well known to the skilled clinician. 
     As used herein when referring to a measurable value such as an amount, a temporal duration, and the like, the term “about” is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. The term “biological” or “biological sample” refers to a sample obtained from an organism or from components (e.g., cells) of an organism. The sample may be of any biological tissue or fluid. Frequently the sample will be a “clinical sample” which is a sample derived from a patient. Such samples include, but are not limited to, bone marrow, cardiac tissue, sputum, blood, lymphatic fluid, blood cells (e.g., white cells), tissue or fine needle biopsy samples, urine, peritoneal fluid, and pleural fluid, or cells therefrom. Biological samples may also include sections of tissues such as frozen sections taken for histological purposes. 
     As used herein, “greater” refers to expression levels which are at least 10% or more, for example, 20%, 30%, 40%, or 50%, 60%, 70%, 80%, 90% higher or more, and/or 1.1 fold, 1.2 fold, 1.4 fold, 1.6 fold, 1.8 fold, 2.0 fold higher or more, and any and all whole or partial increments therebetween, than a control. 
     As used herein, the terms “control,” or “reference” are used interchangeably and refer to a value that is used as a standard of comparison. 
     The term “immunogenicity” as used herein, refers to the innate ability of an antigen or organism to elicit an immune response in an animal when the antigen or organism is administered to the animal. Thus, “enhancing the immunogenicity” refers to increasing the ability of an antigen or organism to elicit an immune response in an animal when the antigen or organism is administered to an animal. The increased ability of an antigen or organism to elicit an immune response can be measured by, among other things, a greater number of antibodies that bind to an antigen or organism, a greater diversity of antibodies to an antigen or organism, a greater number of T-cells specific for an antigen or organism, a greater cytotoxic or helper T-cell response to an antigen or organism, a greater expression of cytokines in response to an antigen, and the like. 
     As used herein, the terms “eliciting an immune response” or “immunizing” refer to the process of generating a B cell and/or a T cell response against a heterologous protein. 
     The term “activation”, as used herein, refers to the state of a cell following sufficient cell surface moiety ligation to induce a noticeable biochemical or morphological change. Within the context of T cells, such activation refers to the state of a T cell that has been sufficiently stimulated to induce cellular proliferation. Activation of a T cell may also induce cytokine production and performance of regulatory or cytolytic effector functions. Within the context of other cells, this term infers either up or down regulation of a particular physico-chemical process. 
     The term “activated T cell” means a T cell that is currently undergoing cell division, cytokine production, performance of regulatory or cytolytic effector functions, and/or has recently undergone the process of “activation.” 
     The term “antigen” or “Ag” as used herein is defined as a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequences or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full-length nucleotide sequence of a gene. It is readily apparent that the present invention includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a biological fluid. 
     “Heterologous antigens” used herein to refer to an antigen that is not endogenous to the organism comprising or expressing an antigen. As an example, a virus vaccine vector comprising or expressing a viral or tumor antigen comprises a heterologous antigen. The term “Heterologous protein” as used herein refers to a protein that elicits a beneficial immune response in a subject (i.e. mammal), irrespective of its source. 
     By the terms “Human Immunodeficiency Virus” or HIV” as used herein is meant any HIV strain or variant that is known in the art or that is heretofore unknown, including without limitation, HIV-1 and HIV-2. HIV-1 is exemplified in certain embodiments disclosed herein. 
     The term “specifically binds”, “selectively binds” or “binding specificity” refers to the ability of the humanized antibodies or binding compounds of the invention to bind to a target epitope with a greater affinity than that which results when bound to a non-target epitope. In certain embodiments, specific binding refers to binding to a target with an affinity that is at least 10, 50, 100, 250, 500, or 1000 times greater than the affinity for a non-target epitope. 
     As used herein, by “combination therapy” is meant that a first agent is administered in conjunction with another agent. “In combination with” or “In conjunction with” refers to administration of one treatment modality in addition to another treatment modality. As such, “in combination with” refers to administration of one treatment modality before, during, or after delivery of the other treatment modality to the individual. Such combinations are considered to be part of a single treatment regimen or regime. 
     “Humoral immunity” or “humoral immune response” both refer to B-cell mediated immunity and are mediated by highly specific antibodies, produced and secreted by B-lymphocytes (B-cells). 
     “Prevention” refers to the use of a pharmaceutical compositions for the vaccination against a disorder. 
     “Adjuvant” refers to a substance that is capable of potentiating the immunogenicity of an antigen. Adjuvants can be one substance or a mixture of substances and function by acting directly on the immune system or by providing a slow release of an antigen. Examples of adjuvants are aluminium salts, polyanions, bacterial glycopeptides and slow release agents as Freund&#39;s incomplete. 
     “Delivery vehicle” refers to a composition that helps to target the antigen to specific cells and to facilitate the effective recognition of an antigen by the immune system. The best-known delivery vehicles are liposomes, virosomes, microparticles including microspheres and nanospheres, polymeres, bacterial ghosts, bacterial polysaccharides, attenuated bacteria, virus like particles, attenuated viruses and ISCOMS. 
     As used herein, the term “expression cassette” means a nucleic acid sequence capable of directing the transcription and/or translation of a heterologous coding sequence. In some embodiments, the expression cassette comprises a promoter sequence operably linked to a sequence encoding a heterologous protein. In some embodiments, the expression cassette further comprises at least one regulatory sequence operably linked to the sequence encoding the heterologous protein. 
     “Incorporated into” or “encapsulated in” refers to an antigenic peptide that is within a delivery vehicle, such as microparticles, bacterial ghosts, attenuated bacteria, virus like particles, attenuated viruses, ISCOMs, liposomes and preferably virosomes. 
     As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that may comprise a protein or peptide&#39;s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof. 
     A “fusion protein” as used herein refers to a protein wherein the protein comprises two or more proteins linked together by peptide bonds or other chemical bonds. The proteins can be linked together directly by a peptide or other chemical bond, or with one or more amino acids between the two or more proteins, referred to herein as a spacer. 
     In the context of the present invention, the following abbreviations for the commonly occurring nucleic acid bases are used. “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine. 
     The term “RNA” as used herein is defined as ribonucleic acid. 
     “Transform”, “transforming”, and “transformation” is used herein to refer to a process of introducing an isolated nucleic acid into the interior of an organism. 
     The term “treatment” as used within the context of the present invention is meant to include therapeutic treatment as well as prophylactic, or suppressive measures for the disease or disorder. As used herein, the term “treatment” and associated terms such as “treat” and “treating” means the reduction of the progression, severity and/or duration of a disease condition or at least one symptom thereof. The term ‘treatment’ therefore refers to any regimen that can benefit a subject. The treatment may be in respect of an existing condition or may be prophylactic (preventative treatment). Treatment may include curative, alleviative or prophylactic effects. References herein to “therapeutic” and “prophylactic” treatments are to be considered in their broadest context. The term “therapeutic” does not necessarily imply that a subject is treated until total recovery. Similarly, “prophylactic” does not necessarily mean that the subject will not eventually contract a disease condition. Thus, for example, the term treatment includes the administration of an agent prior to or following the onset of a disease or disorder thereby preventing or removing all signs of the disease or disorder. As another example, administration of the agent after clinical manifestation of the disease to combat the symptoms of the disease comprises “treatment” of the disease. 
     The term “equivalent,” when used in reference to nucleotide sequences, is understood to refer to nucleotide sequences encoding functionally equivalent polypeptides. Equivalent nucleotide sequences will include sequences that differ by one or more nucleotide substitutions, additions- or deletions, such as allelic variants; and will, therefore, include sequences that differ from the nucleotide sequence of the nucleic acids described herein due to the degeneracy of the genetic code. 
     The term “isolated” as used herein with respect to nucleic acids, such as DNA or RNA, refers to molecules separated from other DNAs or RNAs, respectively that are present in the natural source of the macromolecule. The term isolated as used herein also refers to a nucleic acid or peptide that is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Moreover, an “isolated nucleic acid” is meant to include nucleic acid fragments, which are not naturally occurring as fragments and would not be found in the natural state. The term “isolated” is also used herein to refer to polypeptides, which are isolated from other cellular proteins and is meant to encompass both purified and recombinant polypeptides. An “isolated cell” or “isolated population of cells” is a cell or population of cells that is not present in its natural environment. 
     A “mutation” as used therein is a change in a DNA sequence resulting in an alteration from its natural state. The mutation can comprise a deletion and/or insertion and/or duplication and/or substitution of at least one deoxyribonucleic acid base such as a purine (adenine and/or thymine) and/or a pyrimidine (guanine and/or cytosine). Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. 
     As used herein, the term “nucleic acid” refers to polynucleotides such as deoxyribonucleic acid (DNA), and, where appropriate, ribonucleic acid (RNA). The term should also be understood to include, as equivalents, analogs of either RNA or DNA made from nucleotide analogs, and, as applicable to the embodiment being described, single (sense or antisense) and double-stranded polynucleotides. ESTs, chromosomes, cDNAs, mRNAs, and rRNAs are representative examples of molecules that may be referred to as nucleic acids. 
     As used herein, “operably linked” sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation (polyA) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance secretion of the encoded product. There are numerous expression control sequences, including promoters which are native, constitutive, inducible and/or tissue-specific, are known in the art that may be used in the compositions of the invention. “Operably linked” should be construed to include RNA expression and control sequences in addition to DNA expression and control sequences. 
     The term “promoter” as used herein is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence. 
     As used herein, the term “promoter/regulatory sequence” means a nucleic acid sequence, which is required for expression of a gene product operably linked to the promoter/regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements, which are required for expression of the gene product. The promoter/regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner. 
     A “constitutive” promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell. 
     An “inducible” promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer which corresponds to the promoter is present in the cell. 
     As used herein, the term “pharmaceutical composition” refers to a mixture of at least one compound useful within the invention with other chemical components, such as carriers, stabilizers, diluents, adjuvants, dispersing agents, suspending agents, thickening agents, and/or excipients. The pharmaceutical composition facilitates administration of the compound to an organism. Multiple techniques of administering a compound exist in the art including, but not limited to: intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration. 
     The language “pharmaceutically acceptable carrier” includes a pharmaceutically acceptable salt, pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound(s) of the present invention within or to the subject such that it may perform its intended function. Typically, such compounds are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each salt or carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, and not injurious to the subject. Some examples of materials that may serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer&#39;s solution; ethyl alcohol; phosphate buffer solutions; diluent; granulating agent; lubricant; binder; disintegrating agent; wetting agent; emulsifier; coloring agent; release agent; coating agent; sweetening agent; flavoring agent; perfuming agent; preservative; antioxidant; plasticizer; gelling agent; thickener; hardener; setting agent; suspending agent; surfactant; humectant; carrier; stabilizer; and other non-toxic compatible substances employed in pharmaceutical formulations, or any combination thereof. As used herein, “pharmaceutically acceptable carrier” also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound, and are physiologically acceptable to the subject. Supplementary active compounds may also be incorporated into the compositions. 
     As used herein, the term “effective amount” or “therapeutically effective amount” means the amount of the virus like particle generated from vector of the invention which is required to prevent the particular disease condition, or which reduces the severity of and/or ameliorates the disease condition or at least one symptom thereof or condition associated therewith. 
     A “subject” or “patient,” as used therein, may be a human or non-human mammal. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, feline and murine mammals. Preferably, the subject is human. 
     “Titers” are numerical measures of the concentration of a virus or viral vector compared to a reference sample, where the concentration is determined either by the activity of the virus, or by measuring the number of viruses in a unit volume of buffer. The titer of viral stocks are determined, e.g., by measuring the infectivity of a solution or solutions (typically serial dilutions) of the viruses, e.g., on HeLa cells using the soft agar method (see, Graham &amp; van der Eb (1973) Virology 52:456-467) or by monitoring resistance conferred to cells, e.g., G418 resistance encoded by the virus or vector, or by quantitating the viruses by UV spectrophotometry (see, Chardonnet &amp; Dales (1970) Virology 40:462-477). 
     A “vector” is a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. In the present disclosure, the term “vector” includes an autonomously replicating virus. 
     Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. 
     Description 
     Provided is a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter sequence operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag; wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C; and wherein Gag is from a Chinese HIV clade B. 
     In some embodiments, the expression cassette further comprises at least one regulatory sequence operably linked to the sequence encoding the heterologous protein. 
     In some embodiments, the expression cassette is in the early gene E1 genomic region. 
     In some embodiments, the expression cassette further comprises a chimeric intron and/or CMV enhancer. 
     In some embodiments, an early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. 
     In some embodiments, the entire early gene E3 genomic region is deleted. 
     In further embodiments, the promoter is a constitutive promoter. In yet further embodiments, the promoter is a cytomegalovirus immediate early promoter (CMV). 
     In some embodiments, the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. In some embodiments, the nucleic acid sequence consists of SEQ ID NOs: 6 or 7. 
     Provided is a protein expression system comprising the composition of any one of the previous embodiments, wherein the nucleic acid sequence comprises SEQ ID NOs: 6 or 7. Also provided is a protein expression system comprising the composition of any one of the previous embodiments, wherein the nucleic acid sequence consists of SEQ ID NOs: 6 or 7. Also provided is a protein expression system comprising the composition of any one of the previous embodiments, wherein the heterologous protein encoded by the expression cassette comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5. 
     Also provided is a method of eliciting an immune response in a mammal against a heterologous protein, the method comprising administering to the mammal a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter sequence operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag; wherein gp140 is from a Chinese HIV Clade selected from the group consisting of B, AE, BC and C; and wherein Gag is from a Chinese HIV clade B. 
     In some embodiments, the expression cassette further comprises at least one regulatory sequence operably linked to the sequence encoding the heterologous protein. 
     In some embodiments, the expression cassette is in the early gene E1 genomic region. 
     In some embodiments, the expression cassette further comprises a chimeric intron and/or CMV enhancer. 
     In some embodiments, an early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. 
     In some embodiments, the entire early gene E3 genomic region is deleted. 
     In further embodiments, the promoter is a constitutive promoter. In yet further embodiments, the promoter is a cytomegalovirus immediate early promoter (CMV). 
     Provided is a method of treating and/or preventing HIV in a mammal, the method comprising administering a therapeutically effective amount of a composition encoded by a nucleic acid sequence comprising SEQ ID NOs: 6 or 7. In some embodiments, the nucleic acid sequence consists of SEQ ID NOs: 6 or 7. 
     Provided is a method of vaccinating a mammal against HIV infection, the method comprising administering to the mammal a therapeutically effective amount of the composition of any one of the previous embodiments, wherein administration of the composition elicits an immune response in the mammal. In some embodiments, the composition is administered prophylactically to the mammal. In further embodiments, the composition is administered therapeutically to the mammal. In yet further embodiments, the composition is administered in combination with an adjuvant. 
     Provided is a method of generating a effector and memory T cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of any one of the previous embodiments to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the composition of any one of the previous embodiments at a second, subsequent time period, wherein T memory cells directed against the heterologous protein are reactivated in the mammal. In some embodiments, the composition administered first in (a) and second in (b) comprises a same or a different HIV heterologous protein selected from the group consisting of gp140 and Gag; wherein gp140 is from a Chinese HIV Clade selected from the group consisting of B, AE, BC and C; and wherein Gag is from a Chinese HIV clade B. In further embodiments, the composition administered first in (a) and in (b) is a same or a different serotype selected from the group consisting of AdC6 and AdC7. 
     Provided is a method of generating an adaptive B cell immune response to a heterologous protein in a mammal, the method comprising the steps of: (a) administering the composition of any one of the previous embodiments to a mammal in an amount effective to elicit an immune response in the mammal; (b) administering a second effective amount of the composition of any one of the previous embodiments at a second, subsequent time period, wherein B memory cells directed against the heterologous protein are reactivated in the mammal. 
     In some embodiments, the method further comprises the step of administering an immunogen to the mammal. In further embodiments, the immunogen comprises a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from gp140 derived from any Clade from any source, wherein a B cell immune response is further augmented. In some embodiments, the heterologous protein is from a Chinese Clade or from an African Clade. In some embodiments, the heterologous protein so administered is the same heterologous protein that is expressed in the nucleic acid sequence of a chimpanzee-derived adenovirus vector of any one of the previous embodiments. In some embodiments, the heterologous protein so administered is the same heterologous protein that was administered in step (a) and/or step (b) of any one of the previous methods. In some embodiments, the immunogen further comprises an adjuvant, for example alum. 
     In some embodiments, the immunogen is administered to the mammal after steps (a) and (b). 
     In some embodiments, the mammal is a human. 
     Adenoviral vectors comprising deletions in E1 and/or E3 are disclosed in International Application PCT/US2017/043315 (WO 2018/026547), which is incorporated herein in its entirety. 
     Vaccine compositions comprising adenovirus particles made using the adenovirus vectors disclosed herein can be used to induce immunity in a mammal against one or more encoded heterologous proteins or antigenic portions thereof. Immunity can be induced using the disclosed vaccine compositions or dosage units. Immune responses can be assessed using suitable methods known in the art, as disclosed, for example, in WO2012/02483. 
     Heterologous Gene Expression 
     In one aspect, although the cytomegalovirus immediate early promoter is exemplified herein as the promoter driving expression of the HIV protein, the invention should not be construed to be limited to this promoter sequence. Promoter sequences that are useful in the invention include any promoter that induces high levels of gene expression. Such promoters may include, but are not limited to those disclosed elsewhere herein. 
     In one embodiment, a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. Another example of a suitable promoter is Elongation Growth Factor-1α (EF-1α). However, other constitutive promoter sequences may also be used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Further, the invention should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the invention. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence, which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. 
     In some embodiments, the invention further includes the use of a tissue-specific promoter that drives expression of a given heterologous gene in one or more specific types of cells (e.g., myoglobin promoter, muscle creatine kinase promoter, desmin promoter, mammalian troponin 1 promoter, and skeletal alpha-action promoter). Furthermore, any artificial synthetic promoters known in the art can be used in this invention as these promoters can provide optimal efficiency and stability for the heterologous gene. Additionally, enhancer sequences regulate expression of the gene contained within a vector. Typically, enhancers are bound with protein factors to enhance the transcription of a gene. Enhancers may be located upstream or downstream of the gene it regulates. Enhancers may also be tissue-specific to enhance transcription in a specific cell or tissue type. 
     In order to assess the expression of the heterologous gene of interest, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be infected through the hybrid-virus vectors. In other aspects, the selectable marker may be carried on a separate piece of DNA and used in a co-infection/transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as the neomycin resistant gene and the like. 
     Reporter genes are used for identifying potentially infected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei et al., 2000 FEBS Letters 479: 79-82). 
     It will be apparent to one skilled in the art that the invention is not limited to the nature of the heterologous gene that is expressed by the adenovirus vector of the invention. Any suitable heterologous gene can be used where expression of the gene provides a benefit to the mammal. For example, the heterologous gene may be a viral protein whose expression in a mammal confers immunity to infection by the virus. Similarly, the heterologous gene may be a bacterial antigen, a parasitic antigen, a fungal antigen, a cancer antigen, an antigen involved in a deleterious autoimmune reaction, or any other protein where an immune response directed thereto provides benefit. 
     Heterologous Proteins 
     In the present invention, the adenovirus vector of the invention may encode a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag, wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C, and wherein Gag is from a Chinese HIV clade B. Typically, the heterologous protein is a peptide fragment, polypeptide, protein or fusion protein. Optionally, the heterologous protein is suitable such that cell-mediated immune and humoral responses are induced against it in a mammal following administration of the vector to the mammal. 
     Methods of the Invention 
     The vectors of the invention are useful in a variety of applications useful for immunizing a mammal against disease, and/or treating, preventing or diminishing risk of disease in a mammal. 
     The invention therefore includes a method of immunizing a mammal against a heterologous protein. The method comprises administering to the mammal a composition comprising a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter sequence operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag, wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C, and wherein Gag is from a Chinese HIV clade B, and wherein expression of the heterologous protein induces an immune response in the mammal. 
     In some embodiments, the expression cassette further comprises at least one regulatory sequence operably linked to the sequence encoding the heterologous protein. 
     In some embodiments, the expression cassette is in the early gene E1 genomic region. 
     In some embodiments, the expression cassette further comprises a chimeric intron and/or CMV enhancer. 
     In some embodiments, an early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. 
     In some embodiments, the entire early gene E3 genomic region is deleted. 
     In one embodiment the chimpanzee-derived Ad vector is AdC6. In one embodiment, the AdC6 has Genbank accession number AY530877. In one embodiment the chimpanzee-derived Ad vector is AdC7. In one embodiment, the AdC7 has Genbank accession number AY530878. 
     The invention further includes a method of treating a mammal in need thereof where the method administering a therapeutically effective amount of a composition encoded by a chimpanzee-derived adenovirus vector comprising a nucleic acid sequence comprising SEQ ID NOs: 6 or 7, wherein expression of the heterogeneous gene provides benefit to the mammal. In one aspect, the invention includes a method of generating effector and memory T cell immune responses to a heterologous protein in a mammal. In some embodiments, the nucleic acid sequence consists of SEQ ID NOs: 6 or 7. In another aspect, the invention includes a method of generating an adaptive B cell immune response to a heterologous protein in a mammal. 
     Additionally included in the invention is a method of diminishing the risk that a mammal will develop a disease. The method comprises administering to the mammal a composition comprising a nucleic acid sequence of a chimpanzee-derived adenovirus vector of serotype AdC6 or AdC7, wherein an early gene E1 genomic region is deleted, and wherein the nucleic acid sequence further comprises an expression cassette comprising a promoter sequence operably linked to a sequence encoding a heterologous protein, wherein the heterologous protein is at least one HIV protein selected from the group consisting of gp140 and Gag, wherein gp140 is from a Chinese HIV clade selected from the group consisting of B, AE, BC and C, and wherein Gag is from a Chinese HIV clade B. 
     In some embodiments, the expression cassette further comprises at least one regulatory sequence operably linked to the sequence encoding the heterologous protein. 
     In some embodiments, the expression cassette is in the early gene E1 genomic region. 
     In some embodiments, the expression cassette further comprises a chimeric intron and/or CMV enhancer. 
     In some embodiments, an early gene E3 genomic region consisting of ORF3, ORF4, ORF5, ORF6, and ORF7 is deleted. 
     In some embodiments, the entire early gene E3 genomic region is deleted. 
     Expression of the heterogeneous gene induces an immune response to the heterologous protein encoded thereby in the mammal, thereby diminishing the risk that the mammal will develop a disease (e.g. HIV-1) associated with the heterologous protein. 
     Adenovirus Vector Production 
     Methods of making the adenovirus vector of the invention are described in detail in the Experimental Examples Section herein and in U.S. application Ser. No. 14/190,787 (U.S. Pat. No. 9,624,510) incorporated herein by reference. In general, production, purification and quality control procedures for adenovirus vectors are well established in the art. Once a vector backbone is created, molecular cloning can be used to create an adenoviral plasmid comprising a coding sequence for an antigenic heterologous protein. In some embodiments, the plasmid can be transfected into packaging cells that provide E1 of a suitable adenovirus serotype in trans. Packaging cells are well known in the art, and cells lines such as HEK293 or PERC6 can be used for this purpose. Viral particles are then harvested once plaques become visible. Fresh cells can then be infected to ensure continued replication of the adenovirus. Quality can be assessed using Southern blotting or other methods, such as restriction enzyme mapping, sequencing, and PCR, to confirm the presence of the transgene and the lack of gene rearrangements or undesired deletions. 
     Vaccine compositions comprising adenovirus particles made using the adenovirus vectors disclosed herein can be used to induce immunity against the encoded antigenic protein. Vaccines can be formulated using standard techniques and can comprise, in addition to a replication-incompetent adenovirus vector encoding a desired protein, a pharmaceutically acceptable vehicle, such as phosphate-buffered saline (PBS) or other buffers, as well as other components such as antibacterial and antifungal agents, isotonic and absorption delaying agents, adjuvants, and the like. In some embodiments vaccine compositions are administered in combination with one or more other vaccines. Dosage units of vaccine compositions can be provided. Such dosage units typically comprise 10 8  to 10 11  adenoviral particles (e.g., 10 8 , 5×10 8 , 10 9 , 5×10 9 , 10 10 , 5×10 10 , 10 11 ). In some embodiments, the dosage of 5×10 10  virus particles is of choice. Particularly, this dosage (5×1010) suits best humans in clinical trials. 
     Pharmaceutical Compositions and Formulations. 
     The vector of the invention may be formulated as a pharmaceutical composition. 
     Such a pharmaceutical composition may be in a form suitable for administration to a subject (i.e. mammal), or the pharmaceutical composition may further comprise one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The various components of the pharmaceutical composition may be present in the form of a physiologically acceptable salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. 
     In one embodiment, the pharmaceutical compositions useful for practicing the method of the invention may be administered to deliver a dose of between 10 6  and 10 12  VP. 
     In one embodiment, the pharmaceutical compositions useful for practicing the method of the invention may comprise an adjuvant. Non-limiting examples of suitable are Freund&#39;s complete adjuvant, Freund&#39;s incomplete adjuvant, Quil A, Detox, ISCOMs or squalene. 
     Pharmaceutical compositions that are useful in the methods of the invention may be suitably developed for inhalation, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, intrathecal, intravenous or another route of administration. Other contemplated formulations include projected nanoparticles, liposomal preparations, resealed erythrocytes containing the active ingredient, and immunologically-based formulations. The route(s) of administration is readily apparent to the skilled artisan and depends upon any number of factors including the type and severity of the disease being treated, the type and age of the veterinary or human patient being treated, and the like. 
     Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions suitable for ethical administration to humans, it is understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and perform such modification with merely ordinary, if any, experimentation. Subjects to which administration of the pharmaceutical compositions of the invention is contemplated include, but are not limited to, humans and other primates, mammals including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, and dogs. 
     The composition of the invention may comprise a preservative from about 0.005% to 2.0% by total weight of the composition. The preservative is used to prevent spoilage in the case of exposure to contaminants in the environment. 
     Administration/Dosing 
     The regimen of administration may affect what constitutes an effective amount. For example, the adenovirus vector of the invention may be administered to the subject (i.e. mammal) in a single dose, in several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation. 
     Administration of the compositions of the present invention to a subject, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to treat the disease in the subject. An effective amount of the composition necessary to achieve the intended result will vary and will depend on factors such as the disease to be treated or prevented, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors well-known in the medical arts. In particular embodiments, it is especially advantageous to formulate the composition in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subjects to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the composition and the heterologous protein to be expressed, and the particular therapeutic effect to be achieved. 
     Routes of Administration 
     One skilled in the art will recognize that although more than one route can be used for administration, a particular route can provide a more immediate and more effective reaction than another route. Routes of administration of any of the compositions\ of the invention include inhalation, oral, nasal, rectal, parenteral, sublingual, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal, and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration. 
     Kits 
     In some embodiments a kit is provided for treating, preventing, or ameliorating an a given disease, disorder or condition, or a symptom thereof, as described herein wherein the kit comprises: a) a compound or compositions as described herein; and optionally b) an additional agent or therapy as described herein. The kit can further include instructions or a label for using the kit to treat, prevent, or ameliorate the disease, disorder or condition. In yet other embodiments, the invention extends to kits assays for a given disease, disorder or condition, or a symptom thereof, as described herein. Such kits may, for example, contain the reagents from PCR or other nucleic acid hybridization technology (microarrays) or reagents for immunologically based detection techniques (e.g., ELISpot, ELISA). 
     EXAMPLES 
     The invention is now described with reference to the following Examples. 
     These Examples are provided for the purpose of illustration only and the invention should in no way be construed as being limited to these Examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. 
     Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure. 
     The results of the experiments are now described in the following examples. 
     Methods: 
     According to the Los Alamos database the most prevalent Clades of HIV-1 in China are A/E (29.2%), different types of B/C (30.1%) with mainly 07_B/C (18.7%), B (23.1%) and C (14.7%). Extensive database searches were performed and a panel of Envelope (env) sequences was assembled for induction of antibodies that would be candidates for the development of a comprehensive HIV-1 vaccine for China. In these searches, more recent Chinese isolates for which full-length sequences are available were focused on. Env sequences that carry a K in position 169 and a V in position 172, which, are crucial for binding of broadly neutralizing V2-specific antibodies and for their ADCC activity were preferentially selected. For Gag, a clade B sequence that contains an epitope that is crucial for screening of CD8+ T cell responses in experimental animals was selected. 
     Example 1: Vector Construction and Initial Immunogenicity Testing 
     First Generation Vectors 
     AdC6 and AdC7 vectors expressing gag of HIV clade B and gp140 of HIV clades B, AE, BC and C were generated using an expression cassette without intron and enhancer within E1- and partially E3-deleted vectors. Vectors were titrated for virus content. Vectors were shown to have genetic integrity and were genetically stable upon serial culture. Only the AdC7gp140BC vector induced a gp140-specific B cell response. ( FIG. 1A ) 
     Second Generation Vectors 
     A second set of vectors were constructed using the same AdC backbones (but for AdC7gp140BC) and inserts but the expression cassette was changed by including an intron and enhancer within the expression cassette. Upon rescue, vectors were titrated, and genetic integrity was established. These vectors as shown below were found to be immunogenic. 
     Western blots were conducted for the gag vectors. The first generation gag vector failed to express detectable amounts of gag protein. The second generation gag vectors showed good expression. The Env vectors due to lack of specific antibodies gave ambiguous results. Mass spectrometry may be used to determine expression independent of antibodies, as was determined by use of one of the second generation vectors. 
     Example 2: Immunogenicity of Second Generation Gag Vectors 
     Groups of BALB/c mice were immunized with 10 11  vp of the second generation gag vectors. Their pooled blood was tested 2 weeks later for CD8+ T cell responses by intracellular cytokine staining upon stimulation with the peptide carrying the immunodominant epitope of gag or upon sham stimulation as above ( FIG. 1B ). Mice immunized with either vector showed positive responses. 
     Splenocytes from individual mice were tested 3 days later including staining for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2 and granzyme B (GrmB) ( FIG. 2 ). Upon vaccination, mice showed positive responses for multiple cytokines. The experiment was repeated using lower vector doses of 10 9  and 10 10  vp for the AdC6gag vector and again vectors at these doses induced a detectable CD8 +  T cell response and as is typical for adenovirus vectors a more modest CD4 +  T cell response ( FIG. 3 ). 
     Example 3: First Generation Gp140 Vectors 
     ICR mice were injected with 10 11  vp of the gp140 expressing vectors. They were bled 4 weeks later, and sera were tested by an ELISA on a baculovirus-derived gp140 (Clade C) or BSA coated plates in comparison to sera from naïve mice (negative control) or from mice injected with an already established gp140 vector (positive control). Mice immunized with the AdC7BC developed a detectable antibody response ( FIG. 4 ). Some but not all of the AE immunized mice developed gp140-specific antibodies, and mice immunized with the other vectors failed to seroconvert. 
     Example 4: Second Generation Gp140 Vectors 
     Vectors expressing gp140 (AdC6gp140AE, AdC6gp140B, AdC6gp140C, AdC6gp140BC, AdC7gp140AE, AdC7gp140B, AdC7gp140C), were generated using an expression cassette with intron and an enhancer. Upon titration vectors together with the 1 st  generation AdC7gp140BC vector were injected at 10 11  vp into ICR mice. Their sera were tested 4 weeks later for antibodies to gp140 by ELISAs on plates coated with baculovirus-derived gp140 proteins derived from an early African HIV-1 clade C isolate, a Chinese HIV-1 clade AE isolate, and a Chinese HIV-1 clade BC isolate, the latter two match the sequences of the AdC insert. All vectors induced antibody responses to the 3 env proteins although not all mice responded ( FIG. 4 ). Mice were boosted 5 weeks after priming with the heterologous vectors expressing the same inserts using a vector dose of 10 9  vp per mouse. Individual sera were tested 4 weeks later on clade C, AE and BC gp140 proteins. As shown in  FIG. 5  some of the non-responders became seropositive after the boost, which was most effective in enhancing responses that had been low after priming (e.g., after AdC6BC on clade C protein or AdC7AE on all proteins). The boost was relatively ineffective in some groups ( FIG. 8 ), which may be attributed to the high vector dose used for priming and the 100-fold lower dose used for the boost. 
     Mice primed with the AdC6 vectors and boosted with the AdC7 vectors were boosted again with 2 μg/mouse of a recombinant clade C gp140 protein from the AIDS Reagent Program (protein CN54) diluted 1:1 in alum. As shown in  FIGS. 6 and 9  the protein was very effective at enhancing the vector primed antibody response so that by 5 weeks after this boost all but one mouse in the AE group showed robust antibody responses to the two gp140 derived from Chinese isolates. For comparison, naïve mice were immunized with the same protein in alum; some of these mice developed gp140-specific antibody responses but titers were well below those observed in vector primed mice ( FIG. 9 ). Antibody titers tested on gp140 of the 3 different clades were compared. As shown in  FIG. 10 , responses differed depending on the protein they were tested on. Mice that had high antibody titers against gp140 of one clade did not necessarily have high titers to gp140 of the other clades. By the same token, the data obtained on plates coated with gp140 from the 3 different Clades showed relatively poor correlations ( FIG. 11 ). 
     Example 5: Prime-Boost Regimens 
     Several prime boost regimens were conducted with the AdCgag vectors. In the first set of experiments, priming was conducted with AdC6gag or AdC7gag at 10 9  or 10 10  vp and boosts were given 6 weeks later with heterologous vector given at the same dose. In a follow-up experiment, mixtures of gag and env vectors were used. Boosts were given 6 weeks after the prime. In both experiments, a CD8 +  T cell response to gag was obtained after priming, which paradoxically declined after the boost. The results of the first experiment are shown in  FIG. 12 . Such results were previously obtained with other vectors, indicating that the CD8 +  T cells had remained highly activated after the prime and were therefore susceptible to apoptosis upon re-encounter of their antigen upon the boost. The experiment was repeated using 10 10  vp of Ad6gag for the prime and 10 10  vp of AdC7 for the boost. In the follow-up experiment there was an iterval of 2 months between the prime and the boost. The result was more promising as a small increase in frequencies of gag-specific CD8 +  T cells was observed ( FIG. 13 ). However, frequencies were still well below those routinely seen after prime-boosting with a US-origin clade B gag, indicating that with this particular insert a longer waiting period between priming and boosting is most likely warranted. 
     An experiment was conducted with the vector mixtures in BALB/c mice to assess antibody responses. All other antibody assays had been conducted in ICR mice. When sera against Clade AE and BC proteins were tested, the background responses in naïve mice were extreme high. Background responses against Clade C were less high but still substantial making it virtually impossible to assess if indeed a response had been achieved ( FIG. 14 ). 
     Mixtures of vectors expressing gp140 were tested in ICR mice. Mice were injected with a mixture of the AdC6gP140 Clade C, B, AE and BC vectors at 10 10  vp per vector or with mixtures of the corresponding AdC7 vectors. Mice were bled 2 and 8 weeks later and were then boosted with the heterologous vectors, i.e., AdC6gp140 Clade B, C, AE, BC immune mice were boosted with the corresponding AdC7 vectors and vice versa. Mice were bled 2 weeks later. Antibodies to gp140 of Clade C, BC and AE were determined by ELISA as described elsewhere herein. Although antibody responses were seen in some mice, titers were not as robust as after immunization with vectors expressing gp140 of only one Clade. Furthermore, no increase was seen upon booster immunization. The results are shown in  FIG. 15 . 
     
       
         
           
               
               
            
               
                 Sequences: 
                   
               
               
                 Gp140 Clade AE1: Accession number, JX112804. 
               
               
                 SEQ ID NO: 1 
                   
               
               
                 MRVKGTQMNWPNLWKWGTLILGLVIMCSASDNLWVTVYYGVPVWRDANTTLFCASDAKAH 
                   
               
               
                   
               
               
                 ETEVHNVWATYACVPTDPNPQEIPMENVTENFNMWKNNMVEQMQEDVISLWDQSLKPCVK 
               
               
                   
               
               
                 LTPLCVTLICTNANLTKINSTNSGPKVIGNVTDEVRNCSFNMTTLLTDKKQKVYALFYKL 
               
               
                   
               
               
                 DIVPIDNSNSSEYRLINCNTSVIKQACPKISFDPIPIHYCTPAGYAILKCNDKNFNGTGP 
               
               
                   
               
               
                 CKNVSSVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTNNAKTIIVHLNKAVEINCTR 
               
               
                   
               
               
                 PSNNTRTSIRIGPGQIFYRTGDIIGDIRQAYCEINGTKWNETLRQVAKKLKEQFNNTIKF 
               
               
                   
               
               
                 QPPSGGDLEITMLHFNCRGEFFYCNTTKLFNSTWERNETIKGGNGNGNDTIILPCRIKQI 
               
               
                   
               
               
                 INMWQGAGQAMYAPPISGIINCVSNITGILLTRDGGNTNETAEIFRPGGGNIKDNWRSEL 
               
               
                   
               
               
                 YKYKVVQIEPLGVAPTKAKLTVQARQLLSGIVQQQSNLLRAIEAQQHMLQLTVWGIKQLQ 
               
               
                   
               
               
                 ARILAVESYLKHQQFLGLWGCSNKIICTTAVPWNSSWSNKSYDEIWENMTWIEWEREIGN 
               
               
                   
               
               
                 YTNQIYDILTKSQEQQDKNEKELLELDQWASLWNWFSITKWLW* 
               
               
                   
               
               
                 Gp140 Clade B: Accession number, H1M215399. 
               
               
                 SEQ ID NO: 2 
                   
               
               
                 MRVKGIRKNYQHLWRWGTMLLGMLMICSAAENLWVTVYYGVPVWKEATTTLFCASDAKAY 
                   
               
               
                   
               
               
                 DTEVHNIWATHACVPTDPNPQEVVLGNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCVK 
               
               
                   
               
               
                 LTPLCVTLNCTNLRNTNNTSSNTSNMTEGGEIKNCSFDITTSIRTKVKDYALFYELDIVA 
               
               
                   
               
               
                 IDNTSYRLRQCNTSVITQACPKISFEPIPIHYCTPAGFAILKCNNKTFNGTGPCTNVSTV 
               
               
                   
               
               
                 QCTHRIRPVVSTQLLLNGSLAEEEVVIRSSNFTDNAKVIIVQLKESVEINCTRPNNNTRK 
               
               
                   
               
               
                 SIPLGPGKAWYTTGQIIGDIRQAHCNLSRAKWENTLQQITKKLREQFGNKTIIFNQSSGG 
               
               
                   
               
               
                 DPEVVTHSFNCGGEFFYCNTSQLFNSTWYNNSTWNDTNDTTENSTITLPCRIKQIVNMWQ 
               
               
                   
               
               
                 EVGKAMYAPPIRGQIRCSSNITGLLLTRDGGKNESNTTETFRPGGGDMRDNWRSELYKYK 
               
               
                   
               
               
                 VVKIEPLGVAPTRAKLTVQARQLLSGIVQQQRNLLRAIEAQQHLLQLTVWGIKQLQARVL 
               
               
                   
               
               
                 AVERYLKDQQLLGIWGCSGKLICTTAVPWNVSWSNRSLSEIWDNMTWMEWEREIGNYTKQ 
               
               
                   
               
               
                 IYSLIEESQNQQEKNELELLEWDKWASLWNWFNITNWLW* 
               
               
                   
               
               
                 Gp140 Clade C: Accession number, KF835515. 
               
               
                 SEQ ID NO: 3 
                   
               
               
                 MRVRGTQRNYPQWWIWGILGFWMLMICNVGGNLWVTVYYGVPVWKEATTTLFCASDAKAY 
                   
               
               
                   
               
               
                 ENEVHNVWATHACVPTDPNPQEMVLENVTENFNMWKNEMVNQMHEDVISLWDQSLKPCVK 
               
               
                   
               
               
                 LTPLCVTLKCSNVTLKNNTVNSNETQYRKNCTFNTTTELKNRKQKVSAIFYRIDIVPLGN 
               
               
                   
               
               
                 ESSGNYRLINCNTSAITQACPKVSFDPIPIHYCTPAGYALLKCNNKTFNGTGPCNNVSTV 
               
               
                   
               
               
                 QCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTNNVKTIIVHLNESVEIVCIRPGNNTRQ 
               
               
                   
               
               
                 SIRIGPGQTFYAPGEIIGNIRQAHCNINGTKWNETLQGVGKKLAEHFPNKTIKFKPSSGG 
               
               
                   
               
               
                 DPEITTHSFNCRGEFFYCDTSGLFNSTYNSTYVPNGTESKPNITIQCRIKQIINMWQEVG 
               
               
                   
               
               
                 RAMYAPPIKGSITCKSNITGLLLVRDGGANTTEEIFRPGGGDMRDNWRSELYKYKVVEIK 
               
               
                   
               
               
                 PLGIAPTEAKLTVQARQLLSGIVQQQNNLLKAIEAQQHMLQLTVWGIKQLQTRVLAIERY 
               
               
                   
               
               
                 LKDQQLLGIWGCSGKLICTTAVPWNSSWSNKTQDEIWKNMTWMQWDREINNYTNTIYSLL 
               
               
                   
               
               
                 EESQNQQEKNEKDLLALDSWKNLWNWFDISNWLW* 
               
               
                   
               
               
                 Gp140 Clade BC: Accession number, KC492738. 
               
               
                 SEQ ID NO: 4 
                   
               
               
                 MRVMGIRRNCQHLWRWGIMLLGMLMICSVVGNLWVTVYYGVPVWKEATTTLFCASDAKAY 
                   
               
               
                   
               
               
                 DTEVHNVWATHACVPTDPNPQEMVLENVTENFNMWKNEMVNQMQEDVISLWDQSLKPCVK 
               
               
                   
               
               
                 LTPLCVTLKCKNVSSNSTETPKLRGNSSETYKDEEMKNCSFNATTILRDKKQEVYALFYK 
               
               
                   
               
               
                 LDIAPLLLNSSENSSAYYSLINCNTSAITQACPKVSFDPIPIHYCTPAGYAILKCNDKKF 
               
               
                   
               
               
                 NGTGPCSNVSTVQCTHGIKPVVSTQLLLNGSLAEGEVIIRSKNLTDNAKTIIVQLNRSVE 
               
               
                   
               
               
                 IVCTRPNNNTRKSIRIGPGQTFYATGDIIGDIRQAHCNISEDMWNETLHWVSRKLAEHFP 
               
               
                   
               
               
                 NRTINFTSSSGGDLEIATHSFNCRGEFFYCNTSRLFNGTYMFNGTRGNSSSNSTITIPCR 
               
               
                   
               
               
                 IKQIINMWQQVGRAMYAPPIEGNLTCRSNITGLLLVRDGGDNTNKTEIFRPQGGDMRDNW 
               
               
                   
               
               
                 RSELYKYKVVEIKPLGIAPTTAKLTVQARQLLSGIVQQQSNLLRAIEAQQHLLQLTVWGI 
               
               
                   
               
               
                 KQLQTRVLAIERYLKDQQLLGIWGCSGKLICTTAVPWNSSWSNKTQDEIWNNLTWMQWDK 
               
               
                   
               
               
                 EISNYTDTIYKLLEDSQNQQERNEKDLLALDSWKNLWSWFDITNWLW* 
               
               
                   
               
               
                 HIVgag Clade B: Accession number, JF932500. 
               
               
                 SEQ ID NO: 5 
                   
               
               
                 MGARASVLSGGELDRWEKIRLRPGGKKKYRLKHVVWASRELERFAVNPGLLETSEGCRQI 
                   
               
               
                   
               
               
                 LEQLQPSLQTGSEELRSLYNTIAVLYCVHQKIEIKDTKEALDKIEEEQNKSKKKAQQAAA 
               
               
                   
               
               
                 DTGNNSQVSQNYPIVRNLQGQMVHQPLSPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT 
               
               
                   
               
               
                 PQDLNTMLNTVGGHQAAMQMLRETINEEAAEWDRLHPPQAGPIAPGQIREPRGSDIAGTT 
               
               
                   
               
               
                 SNLQEQIAWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIKQGPKEPFRDYVDRF 
               
               
                   
               
               
                 YKTLRAEQASQDVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPSHKA 
               
               
                   
               
               
                 RILAEAMSQVTNSASVMMQRGNFRNQRKPVKCFNCGKEGHIAKNCRAPRKKGCWKCGKEG 
               
               
                   
               
               
                 HQMKDCTERQANFLGKIWPSHKGRPGNFLQSRPEPTAPPEESFRFGEETTTPSQKQEQID 
               
               
                   
               
               
                 KELYPLASLKSLFGNDPSSQ* 
               
               
                   
               
               
                 1, C6 020 CMV-HIVgp140 AE11 
               
               
                 SEQ ID NO: 6 
                   
               
               
                 catcatcaataatatacctcaaacttttggtgcgcgttaatatgcaaatgagctgtttgaatttg 
                   
               
               
                   
               
               
                 gggagggaggaaggtgattggctgcgggagcggcgaccgttaggggcggggcgggtgacgttttg 
               
               
                   
               
               
                 atgacgtggctatgaggcggagccggtttgcaagttctcgtgggaaaagtgacgtcaaacgaggt 
               
               
                   
               
               
                 gtggtttgaacacggaaatactcaattttcccgcgctctctgacaggaaatgaggtgtttctggg 
               
               
                   
               
               
                 cggatgcaagtgaaaacgggccattttcgcgcgaaaactgaatgaggaagtgaaaatctgagtaa 
               
               
                   
               
               
                 tttcgcgtttatggcagggaggagtatttgccgagggccgagtagactttgaccgattacgtggg 
               
               
                   
               
               
                 ggtttcgattaccgtatttttcacctaaatttccgcgtacggtgtcaaagtccggtgtttttacg 
               
               
                   
               
               
                 tacgatatcatttccccgaaagtgccacctgaccgtaactataacggtcctaaggtagcgaaagc 
               
               
                   
               
               
                 tcagatctcccgatcccctatggtgcactctcagtacaatctgctctgatgccgcatagttaagc 
               
               
                   
               
               
                 cagtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctac 
               
               
                   
               
               
                 aacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgttttgcgctgc 
               
               
                   
               
               
                 ttcgcgatgtacgggccagatatacgcgttgacattgattattgactagttattaatagtaatca 
               
               
                   
               
               
                 attacggggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatgg 
               
               
                   
               
               
                 cccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatag 
               
               
                   
               
               
                 taacgccaatagggactttccattgacgtcaatgggtggagtatttacggtaaactgcccacttg 
               
               
                   
               
               
                 gcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcc 
               
               
                   
               
               
                 cgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtat 
               
               
                   
               
               
                 tagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggttt 
               
               
                   
               
               
                 gactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaa 
               
               
                   
               
               
                 tcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtg 
               
               
                   
               
               
                 tacggtgggaggtctatataagcagagctcgtttagtgaaccgtcagatcactagaagctttatt 
               
               
                   
               
               
                 gcggtagtttatcacagttaaattgctaacgcagtcagtgcttctgacacaacagtctcgaactt 
               
               
                   
               
               
                 aagctgcagaagttggtcgtgaggcactgggcaggtaagtatcaaggttacaagacaggtttaag 
               
               
                   
               
               
                 gagaccaatagaaactgggcttgtcgagacagagaagactcttgcgtttctgataggcacctatt 
               
               
                   
               
               
                 ggtcttactgacatccactttgcctttctctccacaggtgtccactcccagttcaattacagctc 
               
               
                   
               
               
                 ttaaaaggctagagtacttaatacgactcactataggctagcatgagagtgaaggggacacagat 
               
               
                   
               
               
                 gaattggccaaacttgtggaaatgggggactttgatccttgggttggtgatcatgtgtagtgcct 
               
               
                   
               
               
                 cagacaacttgtgggttacagtttattatggagttcctgtgtggagagatgcaaataccacccta 
               
               
                   
               
               
                 ttttgtgcatcagatgccaaagcacatgagacagaagtgcacaatgtctgggccacatatgcctg 
               
               
                   
               
               
                 tgtacccacagatcccaacccacaagaaatacccatggaaaatgtgacagaaaattttaacatgt 
               
               
                   
               
               
                 ggaaaaataacatggtagagcaaatgcaggaggatgtaatcagtttatgggatcaaagtctaaag 
               
               
                   
               
               
                 ccatgtgtaaagttaactcctctctgcgttactttaatttgtaccaatgctaacttgaccaagat 
               
               
                   
               
               
                 caacagtaccaatagcgggcctaaagtaataggaaatgtaacagatgaagtaagaaactgttctt 
               
               
                   
               
               
                 ttaatatgaccacattactaacagataagaagcaaaaggtttatgcacttttttataagcttgat 
               
               
                   
               
               
                 atagtaccaattgataatagtaatagtagtgagtatagattaataaattgtaatacttcagtcat 
               
               
                   
               
               
                 taagcaggcttgtccaaagatatcctttgatccaattcctatacattattgtactccagctggtt 
               
               
                   
               
               
                 atgcgattttaaaatgtaatgataagaatttcaatgggacagggccatgtaaaaatgtcagctca 
               
               
                   
               
               
                 gtacagtgcacacatggaattaagccagtggtctcaactcaattactgttaaatggcagtctagc 
               
               
                   
               
               
                 agaagaagagataataatcagatctgaaaatctcacaaacaatgccaaaaccataatagtgcacc 
               
               
                   
               
               
                 ttaataaggctgtagaaatcaattgtaccagaccctccaacaatacaagaacaagtataagaata 
               
               
                   
               
               
                 ggaccaggacaaatattttatagaacaggagacataataggagatataagacaagcatattgtga 
               
               
                   
               
               
                 aattaatggaacaaaatggaatgaaactttaagacaggtagcaaaaaaattaaaagagcaattta 
               
               
                   
               
               
                 ataacacaataaaattccagccaccctcaggaggagatctagaaattacaatgcttcattttaat 
               
               
                   
               
               
                 tgtagaggggaatttttctattgcaatacaacaaaactgttcaatagtacttgggaaagaaatga 
               
               
                   
               
               
                 gaccataaaagggggtaatggcaatggcaatgacactatcatacttccatgcaggataaagcaaa 
               
               
                   
               
               
                 tcataaacatgtggcaaggagcaggacaagcaatgtatgctcctcccatcagtggaataattaac 
               
               
                   
               
               
                 tgtgtatcaaatattacaggaatactattgacaagagatggtggtaatactaatgaaactgccga 
               
               
                   
               
               
                 gatcttcagacctggaggaggaaatataaaggacaattggagaagtgaattatataaatataaag 
               
               
                   
               
               
                 tagtacaaattgaaccactaggagtagcacccaccaaggcaaagctgacggtacaggccagacaa 
               
               
                   
               
               
                 ttattgtctggtatagtgcaacagcaaagcaatttgctgagggctatagaggcgcagcagcatat 
               
               
                   
               
               
                 gttgcaactcacagtctggggcattaaacagctccaggcaagaatcctggctgtggaaagctacc 
               
               
                   
               
               
                 taaagcatcaacagttcctaggactttggggctgctctaacaaaattatctgcaccactgctgta 
               
               
                   
               
               
                 ccctggaattcctcttggagtaataaatcttatgatgagatttgggaaaatatgacatggataga 
               
               
                   
               
               
                 atgggagagagaaattggcaattacacaaaccaaatatatgatatacttacaaaatcgcaggaac 
               
               
                   
               
               
                 agcaggacaaaaatgaaaaggaactgttggaattggatcaatgggcaagtctgtggaattggttt 
               
               
                   
               
               
                 agcataacaaaatggctgtggtaatgtacaagtaaagcggccgccactgtgctggatgatccgag 
               
               
                   
               
               
                 ctcggtacctctagagtcgacccgggcggccaaaccgctgatcagcctcgactgtgccttctagt 
               
               
                   
               
               
                 tgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccac 
               
               
                   
               
               
                 tgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg 
               
               
                   
               
               
                 ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat 
               
               
                   
               
               
                 gcggtgggctctatggcttctgaggcggaaagaaccagcagatctgcagatctgaattcatctat 
               
               
                   
               
               
                 gtcgggtgcggagaaagaggtaatgaaatggcattatgggtattatgggtctgcattaatgaatc 
               
               
                   
               
               
                 ggtcagatatcgacatatgctggccaccgtgcatgtggcctcgcacccccgcaagacatggcccg 
               
               
                   
               
               
                 agttcgagcacaacgtcatgacccgctgcaatgtgcacctgggctcccgccgaggcatgttcatg 
               
               
                   
               
               
                 ccctaccagtgcaacatgcaatttgtgaaggtgctgctggagcccgatgccatgtccagagtgag 
               
               
                   
               
               
                 cctgacgggggtgtttgacatgaatgtggagctgtggaaaattctgagatatgatgaatccaaga 
               
               
                   
               
               
                 ccaggtgccgggcctgcgaatgcggaggcaagcacgccaggcttcagcccgtgtgtgtggaggtg 
               
               
                   
               
               
                 acggaggacctgcgacccgatcatttggtgttgtcctgcaacgggacggagttcggctccagcgg 
               
               
                   
               
               
                 ggaagaatctgactagagtgagtagtgtttggggctgggtgtgagcctgcatgaggggcagaatg 
               
               
                   
               
               
                 actaaaatctgtggttttctgtgtgttgcagcagcatgagcggaagcgcctcctttgagggaggg 
               
               
                   
               
               
                 gtattcagcccttatctgacggggcgtctcccctcctgggcgggagtgcgtcagaatgtgatggg 
               
               
                   
               
               
                 atccacggtggacggccggcccgtgcagcccgcgaactcttcaaccctgacctacgcgaccctga 
               
               
                   
               
               
                 gctcctcgtccgtggacgcagctgccgccgcagctgctgcttccgccgccagcgccgtgcgcgga 
               
               
                   
               
               
                 atggccctgggcgccggctactacagctctctggtggccaactcgagttccaccaataatcccgc 
               
               
                   
               
               
                 cagcctgaacgaggagaagctgctgctgctgatggcccagctcgaggccctgacccagcgcctgg 
               
               
                   
               
               
                 gcgagctgacccagcaggtggctcagctgcaggcggagacgcgggccgcggttgccacggtgaaa 
               
               
                   
               
               
                 accaaataaaaaatgaatcaataaataaacggagacggttgttgattttaacacagagtcttgaa 
               
               
                   
               
               
                 tctttatttgatttttcgcgcgcggtaggccctggaccaccggtctcgatcattgagcacccggt 
               
               
                   
               
               
                 ggatcttttccaggacccggtagaggtgggcttggatgttgaggtacatgggcatgagcccgtcc 
               
               
                   
               
               
                 cgggggtggaggtagctccattgcagggcctcgtgctcggggatggtgttgtaaatcacccagtc 
               
               
                   
               
               
                 atagcaggggcgcagggcgtggtgctgcacgatgtccttgaggaggagactgatggccacgggca 
               
               
                   
               
               
                 gccccttggtgtaggtgttgacgaacctgttgagctgggagggatgcatgcggggggagatgaga 
               
               
                   
               
               
                 tgcatcttggcctggatcttgagattggcgatgttcccgcccagatcccgccgggggttcatgtt 
               
               
                   
               
               
                 gtgcaggaccaccagcacggtgtatccggtgcacttggggaatttgtcatgcaacttggaaggga 
               
               
                   
               
               
                 aggcgtgaaagaatttggagacgcccttgtgaccgcccaggttttccatgcactcatccatgatg 
               
               
                   
               
               
                 atggcgatgggcccgtgggcggcggcctgggcaaagacgtttcgggggtcggacacatcgtagtt 
               
               
                   
               
               
                 gtggtcctgggtgagctcgtcataggccattttaatgaatttggggcggagggtgcccgactggg 
               
               
                   
               
               
                 ggacgaaggtgccctcgatcccgggggcgtagttgccctcgcagatctgcatctcccaggcaagc 
               
               
                   
               
               
                 aggttccggagcagctgggacttgccgcaaccggtggggccgtagatgaccccgatgaccggctg 
               
               
                   
               
               
                 caggtggtagttgagggagagacagctgccgtcctcgcggaggaggggggccacctcgttcatca 
               
               
                   
               
               
                 tctcgcgcacatgcatgttctcgcgcacgagttccgccaggaggcgctcgccccccagcgagagg 
               
               
                   
               
               
                 agctcttgcagcgaggcgaagtttttcagcggcttgagtccgtcggccatgggcattttggagag 
               
               
                   
               
               
                 ggtctgttgcaagagttccagacggtcccagagctcggtgatgtgctctagggcatctcgatcca 
               
               
                   
               
               
                 gcagacctcctcgtttcgcgggttggggcgactgcgggagtagggcaccaggcgatgggcgtcca 
               
               
                   
               
               
                 gcgaggccagggtccggtccttccagggccgcagggtccgcgtcagcgtggtctccgtcacggtg 
               
               
                   
               
               
                 aaggggtgcgcgccgggctgggcgcttgcgagggtgcgcttcaggctcatccggctggtcgagaa 
               
               
                   
               
               
                 ccgctcccggtcggcgccctgcgcgtcggccaggtagcaattgagcatgagttcgtagttgagcg 
               
               
                   
               
               
                 cctcggccgcgtggcccttggcgcggagcttacctttggaagtgtgtccgcagacgggacagagg 
               
               
                   
               
               
                 agggacttgagggcgtagagcttgggggcgaggaagacggactcgggggcgtaggcgtccgcgcc 
               
               
                   
               
               
                 gcagctggcgcagacggtctcgcactccacgagccaggtgaggtcggggcggttggggtcaaaaa 
               
               
                   
               
               
                 cgaggtttcctccgtgctttttgatgcgtttcttacctctggtctccatgagctcgtgtccccgc 
               
               
                   
               
               
                 tgggtgacaaagaggctgtccgtgtccccgtagaccgactttatgggccggtcctcgagcggggt 
               
               
                   
               
               
                 gccgcggtcctcgtcgtagaggaaccccgcccactccgagacgaaggcccgggtccaggccagca 
               
               
                   
               
               
                 cgaaggaggccacgtgggaggggtagcggtcgttgtccaccagcgggtccaccttctccagggta 
               
               
                   
               
               
                 tgcaagcacatgtccccctcgtccacatccaggaaggtgattggcttgtaagtgtaggccacgtg 
               
               
                   
               
               
                 accgggggtcccggccgggggggtataaaagggggcgggcccctgctcgtcctcactgtcttccg 
               
               
                   
               
               
                 gatcgctgtccaggagcgccagctgttggggtaggtattccctctcgaaggcgggcatgacctcg 
               
               
                   
               
               
                 gcactcaggttgtcagtttctagaaacgaggaggatttgatattgacggtgccgttggagacgcc 
               
               
                   
               
               
                 tttcatgagcccctcgtccatttggtcagaaaagacgatctttttgttgtcgagcttggtggcga 
               
               
                   
               
               
                 aggagccgtagagggcgttggagagcagcttggcgatggagcgcatggtctggttcttttccttg 
               
               
                   
               
               
                 tcggcgcgctccttggcggcgatgttgagctgcacgtactcgcgcgccacgcacttccattcggg 
               
               
                   
               
               
                 gaagacggtggtgagctcgtcgggcacgattctgacccgccagccgcggttgtgcagggtgatga 
               
               
                   
               
               
                 ggtccacgctggtggccacctcgccgcgcaggggctcgttggtccagcagaggcgcccgcccttg 
               
               
                   
               
               
                 cgcgagcagaaggggggcagcgggtccagcatgagctcgtcgggggggtcggcgtccacggtgaa 
               
               
                   
               
               
                 gatgccgggcaggagctcggggtcgaagtagctgatgcaggtgcccagattgtccagcgccgctt 
               
               
                   
               
               
                 gccagtcgcgcacggccagcgcgcgctcgtaggggctgaggggcgtgccccagggcatggggtgc 
               
               
                   
               
               
                 gtgagcgcggaggcgtacatgccgcagatgtcgtagacgtagaggggctcctcgaggacgccgat 
               
               
                   
               
               
                 gtaggtggggtagcagcgccccccgcggatgctggcgcgcacgtagtcgtacagctcgtgcgagg 
               
               
                   
               
               
                 gcgcgaggagccccgtgccgaggttggagcgttgcggcttttcggcgcggtagacgatctggcgg 
               
               
                   
               
               
                 aagatggcgtgggagttggaggagatggtgggcctttggaagatgttgaagtgggcgtggggcag 
               
               
                   
               
               
                 gccgaccgagtccctgatgaagtgggcgtaggagtcctgcagcttggcgacgagctcggcggtga 
               
               
                   
               
               
                 cgaggacgtccagggcgcagtagtcgagggtctcttggatgatgtcatacttgagctggcccttc 
               
               
                   
               
               
                 tgcttccacagctcgcggttgagaaggaactcttcgcggtccttccagtactcttcgagggggaa 
               
               
                   
               
               
                 cccgtcctgatcggcacggtaagagcccaccatgtagaactggttgacggccttgtaggcgcagc 
               
               
                   
               
               
                 agcccttctccacggggagggcgtaagcttgcgcggccttgcgcagggaggtgtgggtgagggcg 
               
               
                   
               
               
                 aaggtgtcgcgcaccatgaccttgaggaactggtgcttgaagtcgaggtcgtcgcagccgccctg 
               
               
                   
               
               
                 ctcccagagttggaagtccgtgcgcttcttgtaggcggggttaggcaaagcgaaagtaacatcgt 
               
               
                   
               
               
                 tgaagaggatcttgcccgcgcggggcatgaagttgcgagtgatgcggaaaggctggggcacctcg 
               
               
                   
               
               
                 gcccggttgttgatgacctgggcggcgaggacgatctcgtcgaagccgttgatgttgtgcccgac 
               
               
                   
               
               
                 gatgtagagttccacgaatcgcgggcggcccttgacgtggggcagcttcttgagctcgtcgtagg 
               
               
                   
               
               
                 tgagctcggcggggtcgctgagcccgtgctgctcgagggcccagtcggcgacgtgggggttggcg 
               
               
                   
               
               
                 ctgaggaaggaagtccagagatccacggccagggcggtctgcaagcggtcccggtactgacggaa 
               
               
                   
               
               
                 ctgttggcccacggccattttttcgggggtgacgcagtagaaggtgcgggggtcgccgtgccagc 
               
               
                   
               
               
                 ggtcccacttgagctggagggcgaggtcgtgggcgagctcgacgagcggcgggtccccggagagt 
               
               
                   
               
               
                 ttcatgaccagcatgaaggggacgagctgcttgccgaaggaccccatccaggtgtaggtttccac 
               
               
                   
               
               
                 atcgtaggtgaggaagagcctttcggtgcgaggatgcgagccgatggggaagaactggatctcct 
               
               
                   
               
               
                 gccaccagttggaggaatggctgttgatgtgatggaagtagaaatgccgacggcgcgccgagcac 
               
               
                   
               
               
                 tcgtgcttgtgtttatacaagcgtccgcagtgctcgcaacgctgcacgggatgcacgtgctgcac 
               
               
                   
               
               
                 gagctgtacctgggttcctttggcgaggaatttcagtgggcagtggagcgctggcggctgcatct 
               
               
                   
               
               
                 cgtgctgtactacgtcttggccatcggcgtggccatcgtctgcctcgatggtggtcatgctgacg 
               
               
                   
               
               
                 agcccgcgcgggaggcaggtccagacctcggctcggacgggtcggagagcgaggacgagggcgcg 
               
               
                   
               
               
                 caggccggagctgtccagggtcctgagacgctgcggagtcaggtcagtgggcagcggcggcgcgc 
               
               
                   
               
               
                 ggttgacttgcaggagcttttccagggcgcgcgggaggtccagatggtacttgatctccacggcg 
               
               
                   
               
               
                 ccgttggtggctacgtccacggcttgcagggtgccgtgcccctggggcgccaccaccgtgccccg 
               
               
                   
               
               
                 tttcttcttgggcgctgcttccatgtcggtcagaagcggcggcgaggacgcgcgccgggcggcag 
               
               
                   
               
               
                 gggcggctcggggcccggaggcaggggcggcaggggcacgtcggcgccgcgcgcgggcaggttct 
               
               
                   
               
               
                 ggtactgcgcccggagaagactggcgtgagcgacgacgcgacggttgacgtcctggatctgacgc 
               
               
                   
               
               
                 ctctgggtgaaggccacgggacccgtgagtttgaacctgaaagagagttcgacagaatcaatctc 
               
               
                   
               
               
                 ggtatcgttgacggcggcctgccgcaggatctcttgcacgtcgcccgagttgtcctggtaggcga 
               
               
                   
               
               
                 tctcggtcatgaactgctcgatctcctcctcctgaaggtctccgcggccggcgcgctcgacggtg 
               
               
                   
               
               
                 gccgcgaggtcgttggagatgcggcccatgagctgcgagaaggcgttcatgccggcctcgttcca 
               
               
                   
               
               
                 gacgcggctgtagaccacggctccgtcggggtcgcgcgcgcgcatgaccacctgggcgaggttga 
               
               
                   
               
               
                 gctcgacgtggcgcgtgaagaccgcgtagttgcagaggcgctggtagaggtagttgagcgtggtg 
               
               
                   
               
               
                 gcgatgtgctcggtgacgaagaagtacatgatccagcggcggagcggcatctcgctgacgtcgcc 
               
               
                   
               
               
                 cagggcttccaagcgttccatggcctcgtagaagtccacggcgaagttgaaaaactgggagttgc 
               
               
                   
               
               
                 gcgccgagacggtcaactcctcctccagaagacggatgagctcggcgatggtggcgcgcacctcg 
               
               
                   
               
               
                 cgctcgaaggccccggggggctcctcttccatctcctcctcttcctcctccactaacatctcttc 
               
               
                   
               
               
                 tacttcctcctcaggaggcggtggcgggggaggggccctgcgtcgccggcggcgcacgggcagac 
               
               
                   
               
               
                 ggtcgatgaagcgctcgatggtctccccgcgccggcgacgcatggtctcggtgacggcgcgcccg 
               
               
                   
               
               
                 tcctcgcggggccgcagcatgaagacgccgccgcgcatctccaggtggccgccgggggggtctcc 
               
               
                   
               
               
                 gttgggcagggagagggcgctgacgatgcatcttatcaattgacccgtagggactccgcgcaagg 
               
               
                   
               
               
                 acctgagcgtctcgagatccacgggatccgaaaaccgctgaacgaaggcttcgagccagtcgcag 
               
               
                   
               
               
                 tcgcaaggtaggctgagcccggtttcttgttcttcgggtatttggtcgggaggcgggcgggcgat 
               
               
                   
               
               
                 gctgctggtgatgaagttgaagtaggcggtcctgagacggcggatggtggcgaggagcaccaggt 
               
               
                   
               
               
                 ccttgggcccggcttgctggatgcgcagacggtcggccatgccccaggcgtggtcctgacacctg 
               
               
                   
               
               
                 gcgaggtccttgtagtagtcctgcatgagccgctccacgggcacctcctcctcgcccgcgcggcc 
               
               
                   
               
               
                 gtgcatgcgcgtgagcccgaacccgcgctgcggctggacgagcgccaggtcggcgacgacgcgct 
               
               
                   
               
               
                 cggtgaggatggcctgctggatctgggtgagggtggtctggaagtcgtcgaagtcgacgaagcgg 
               
               
                   
               
               
                 tggtaggctccggtgttgatggtgtaggagcagttggccatgacggaccagttgacggtctggtg 
               
               
                   
               
               
                 gccgggtcgcacgagctcgtggtacttgaggcgcgagtaggcgcgcgtgtcgaagatgtagtcgt 
               
               
                   
               
               
                 tgcaggcgcgcacgaggtactggtatccgacgaggaagtgcggcggcggctggcggtagagcggc 
               
               
                   
               
               
                 catcgctcggtggcgggggcgccgggcgcgaggtcctcgagcatgaggcggtggtagccgtagat 
               
               
                   
               
               
                 gtacctggacatccaggtgatgccggcggcggtggtggaggcgcgcgggaactcgcggacgcggt 
               
               
                   
               
               
                 tccagatgttgcgcagcggcaggaagtagttcatggtggccgcggtctggcccgtgaggcgcgcg 
               
               
                   
               
               
                 cagtcgtggatgctctagacatacgggcaaaaacgaaagcggtcagcggctcgactccgtggcct 
               
               
                   
               
               
                 ggaggctaagcgaacgggttgggctgcgcgtgtaccccggttcgaatctcgaatcaggctggagc 
               
               
                   
               
               
                 cgcagctaacgtggtactggcactcccgtctcgacccaagcctgctaacgaaacctccaggatac 
               
               
                   
               
               
                 ggaggcgggtcgttttttggccttggtcgctggtcatgaaaaactagtaagcgcggaaagcggcc 
               
               
                   
               
               
                 gcccgcgatggctcgctgccgtagtctggagaaagaatcgccagggttgcgttgcggtgtgcccc 
               
               
                   
               
               
                 ggttcgagcctcagcgctcggcgccggccggattccgcggctaacgtgggcgtggctgccccgtc 
               
               
                   
               
               
                 gtttccaagaccccttagccagccgacttctccagttacggagcgagcccctctttttttttctt 
               
               
                   
               
               
                 gtgtttttgccagatgcatcccgtactgcggcagatgcgcccccaccctccaccacaaccgcccc 
               
               
                   
               
               
                 taccgcagcagcagcaacagccggcgcttctgcccccgccccagcagcagccagccactaccgcg 
               
               
                   
               
               
                 gcggccgccgtgagcggagccggcgttcagtatgacctggccttggaagagggcgaggggctggc 
               
               
                   
               
               
                 gcggctgggggcgtcgtcgccggagcggcacccgcgcgtgcagatgaaaagggacgctcgcgagg 
               
               
                   
               
               
                 cctacgtgcccaagcagaacctgttcagagacaggagcggcgaggagcccgaggagatgcgcgcc 
               
               
                   
               
               
                 tcccgcttccacgcggggcgggagctgcggcgcggcctggaccgaaagcgggtgctgagggacga 
               
               
                   
               
               
                 ggatttcgaggcggacgagctgacggggatcagccccgcgcgcgcgcacgtggccgcggccaacc 
               
               
                   
               
               
                 tggtcacggcgtacgagcagaccgtgaaggaggagagcaacttccaaaaatccttcaacaaccac 
               
               
                   
               
               
                 gtgcgcacgctgatcgcgcgcgaggaggtgaccctgggcctgatgcacctgtgggacctgctgga 
               
               
                   
               
               
                 ggccatcgtgcagaaccccacgagcaagccgctgacggcgcagctgtttctggtggtgcagcaca 
               
               
                   
               
               
                 gtcgggacaacgagacgttcagggaggcgctgctgaatatcaccgagcccgagggccgctggctc 
               
               
                   
               
               
                 ctggacctggtgaacattttgcagagcatcgtggtgcaggagcgcgggctgccgctgtccgagaa 
               
               
                   
               
               
                 gctggcggccatcaacttctcggtgctgagtctgggcaagtactacgctaggaagatctacaaga 
               
               
                   
               
               
                 ccccgtacgtgcccatagacaaggaggtgaagatcgacgggttttacatgcgcatgaccctgaaa 
               
               
                   
               
               
                 gtgctgaccctgagcgacgatctgggggtgtaccgcaacgacaggatgcaccgcgcggtgagcgc 
               
               
                   
               
               
                 cagccgccggcgcgagctgagcgaccaggagctgatgcacagcctgcagcgggccctgaccgggg 
               
               
                   
               
               
                 ccgggaccgagggggagagctactttgacatgggcgcggacctgcgctggcagcccagccgccgg 
               
               
                   
               
               
                 gccttggaagctgccggcggttccccctacgtggaggaggtggacgatgaggaggaggagggcga 
               
               
                   
               
               
                 gtacctggaagactgatggcgcgaccgtatttttgctagatgcagcaacagccaccgccgccgcc 
               
               
                   
               
               
                 tcctgatcccgcgatgcgggcggcgctgcagagccagccgtccggcattaactcctcggacgatt 
               
               
                   
               
               
                 ggacccaggccatgcaacgcatcatggcgctgacgacccgcaatcccgaagcctttagacagcag 
               
               
                   
               
               
                 cctcaggccaaccggctctcggccatcctggaggccgtggtgccctcgcgctcgaaccccacgca 
               
               
                   
               
               
                 cgagaaggtgctggccatcgtgaacgcgctggtggagaacaaggccatccgcggtgacgaggccg 
               
               
                   
               
               
                 ggctggtgtacaacgcgctgctggagcgcgtggcccgctacaacagcaccaacgtgcagacgaac 
               
               
                   
               
               
                 ctggaccgcatggtgaccgacgtgcgcgaggcggtgtcgcagcgcgagcggttccaccgcgagtc 
               
               
                   
               
               
                 gaacctgggctccatggtggcgctgaacgccttcctgagcacgcagcccgccaacgtgccccggg 
               
               
                   
               
               
                 gccaggaggactacaccaacttcatcagcgcgctgcggctgatggtggccgaggtgccccagagc 
               
               
                   
               
               
                 gaggtgtaccagtcggggccggactacttcttccagaccagtcgccagggcttgcagaccgtgaa 
               
               
                   
               
               
                 cctgagccaggctttcaagaacttgcagggactgtggggcgtgcaggccccggtcggggaccgcg 
               
               
                   
               
               
                 cgacggtgtcgagcctgctgacgccgaactcgcgcctgctgctgctgctggtggcgcccttcacg 
               
               
                   
               
               
                 gacagcggcagcgtgagccgcgactcgtacctgggctacctgcttaacctgtaccgcgaggccat 
               
               
                   
               
               
                 cggacaggcgcacgtggacgagcagacctaccaggagatcacccacgtgagccgcgcgctgggcc 
               
               
                   
               
               
                 aggaggacccgggcaacctggaggccaccctgaacttcctgctgaccaaccggtcgcagaagatc 
               
               
                   
               
               
                 ccgccccagtacgcgctgagcaccgaggaggagcgcatcctgcgctacgtgcagcagagcgtggg 
               
               
                   
               
               
                 gctgttcctgatgcaggagggggccacgcccagcgcggcgctcgacatgaccgcgcgcaacatgg 
               
               
                   
               
               
                 agcccagcatgtacgcccgcaaccgcccgttcatcaataagctgatggactacttgcatcgggcg 
               
               
                   
               
               
                 gccgccatgaactcggactactttaccaacgccatcttgaacccgcactggctcccgccgcccgg 
               
               
                   
               
               
                 gttctacacgggcgagtacgacatgcccgaccccaacgacgggttcctgtgggacgacgtggaca 
               
               
                   
               
               
                 gcagcgtgttctcgccgcgtccaggaaccaatgccgtgtggaagaaagagggcggggaccggcgg 
               
               
                   
               
               
                 ccgtcctcggcgctgtccggtcgcgcgggtgctgccgcggcggtgcccgaggccgccagcccctt 
               
               
                   
               
               
                 cccgagcctgcccttttcgctgaacagcgtgcgcagcagcgagctgggtcggctgacgcgaccgc 
               
               
                   
               
               
                 gcctgctgggcgaggaggagtacctgaacgactccttgttgaggcccgagcgcgagaagaacttc 
               
               
                   
               
               
                 cccaataacgggatagagagcctggtggacaagatgagccgctggaagacgtacgcgcacgagca 
               
               
                   
               
               
                 cagggacgagccccgagctagcagcgcaggcacccgtagacgccagcggcacgacaggcagcggg 
               
               
                   
               
               
                 gactggtgtgggacgatgaggattccgccgacgacagcagcgtgttggacttgggtgggagtggt 
               
               
                   
               
               
                 ggtaacccgttcgctcacctgcgcccccgtatcgggcgcctgatgtaagaatctgaaaaaataaa 
               
               
                   
               
               
                 agacggtactcaccaaggccatggcgaccagcgtgcgttcttctctgttgtttgtagtagtatga 
               
               
                   
               
               
                 tgaggcgcgtgtacccggagggtcctcctccctcgtacgagagcgtgatgcagcaggcggtggcg 
               
               
                   
               
               
                 gcggcgatgcagcccccgctggaggcgccttacgtgcccccgcggtacctggcgcctacggaggg 
               
               
                   
               
               
                 gcggaacagcattcgttactcggagctggcacccttgtacgataccacccggttgtacctggtgg 
               
               
                   
               
               
                 acaacaagtcggcagacatcgcctcgctgaactaccagaacgaccacagcaacttcctgaccacc 
               
               
                   
               
               
                 gtggtgcagaacaacgatttcacccccacggaggccagcacccagaccatcaactttgacgagcg 
               
               
                   
               
               
                 ctcgcggtggggcggccagctgaaaaccatcatgcacaccaacatgcccaacgtgaacgagttca 
               
               
                   
               
               
                 tgtacagcaacaagttcaaggcgcgggtgatggtctcgcgcaagacccccaacggggtggatgat 
               
               
                   
               
               
                 gattatgatggtagtcaggacgagctgacctacgagtgggtggagtttgagctgcccgagggcaa 
               
               
                   
               
               
                 cttctcggtgaccatgaccatcgatctgatgaacaacgccatcatcgacaactacttggcggtgg 
               
               
                   
               
               
                 ggcggcagaacggggtgctggagagcgacatcggcgtgaagttcgacacgcgcaacttccggctg 
               
               
                   
               
               
                 ggctgggaccccgtgaccgagctggtgatgccgggcgtgtacaccaacgaggccttccaccccga 
               
               
                   
               
               
                 catcgtcctgctgcccggctgcggcgtggacttcaccgagagccgcctcagcaacctgctgggca 
               
               
                   
               
               
                 tccgcaagcggcagcccttccaggagggcttccagatcctgtacgaggacctggaggggggcaac 
               
               
                   
               
               
                 atccccgcgctcttggatgtcgaagcctacgagaaaagcaaggaggatagcaccgccgcggcgac 
               
               
                   
               
               
                 cgcagccgtggccaccgcctctaccgaggtgcggggcgataattttgctagcgctgcggcagcgg 
               
               
                   
               
               
                 ccgaggcggctgaaaccgaaagtaagatagtcatccagccggtggagaaggacagcaaggacagg 
               
               
                   
               
               
                 agctacaacgtgctcgcggacaagaaaaacaccgcctaccgcagctggtacctggcctacaacta 
               
               
                   
               
               
                 cggcgaccccgagaagggcgtgcgctcctggacgctgctcaccacctcggacgtcacctgcggcg 
               
               
                   
               
               
                 tggagcaagtctactggtcgctgcccgacatgatgcaagacccggtcaccttccgctccacgcgt 
               
               
                   
               
               
                 caagttagcaactacccggtggtgggcgccgagctcctgcccgtctactccaagagcttcttcaa 
               
               
                   
               
               
                 cgagcaggccgtctactcgcagcagctgcgcgccttcacctcgctcacgcacgtcttcaaccgct 
               
               
                   
               
               
                 tccccgagaaccagatcctcgtccgcccgcccgcgcccaccattaccaccgtcagtgaaaacgtt 
               
               
                   
               
               
                 cctgctctcacagatcacgggaccctgccgctgcgcagcagtatccggggagtccagcgcgtgac 
               
               
                   
               
               
                 cgtcactgacgccagacgccgcacctgcccctacgtctacaaggccctgggcgtcgcccagcaag 
               
               
                   
               
               
                 atgtacggaggcgctcgccaacgctccacgcaacaccccgtgcgcgtgcgcgggcacttccgcgc 
               
               
                   
               
               
                 tccctggggcgccctcaagggccgcgtgcgctcgcgcaccaccgtcgacgacgtgatcgaccagg 
               
               
                   
               
               
                 tggtggccgacgcgcgcaactacacgcccgccgccgcgcccgtctccaccgtggacgccgtcatc 
               
               
                   
               
               
                 gacagcgtggtggccgacgcgcgccggtacgcccgcaccaagagccggcggcggcgcatcgcccg 
               
               
                   
               
               
                 gcggcaccggagcacccccgccatgcgcgcggcgcgagccttgctgcgcagggccaggcgcacgg 
               
               
                   
               
               
                 gacgcagggccatgctcagggcggccagacgcgcggcctccggcagcagcagcgccggcaggacc 
               
               
                   
               
               
                 cgcagacgcgcggccacggcggcggcggcggccatcgccagcatgtcccgcccgcggcgcggcaa 
               
               
                   
               
               
                 cgtgtactgggtgcgcgacgccgccaccggtgtgcgcgtgcccgtgcgcacccgcccccctcgca 
               
               
                   
               
               
                 cttgaagatgctgacttcgcgatgttgatgtgtcccagcggcgaggaggatgtccaagcgcaaat 
               
               
                   
               
               
                 acaaggaagagatgctccaggtcatcgcgcctgagatctacggccccgcggcggcggtgaaggag 
               
               
                   
               
               
                 gaaagaaagccccgcaaactgaagcgggtcaaaaaggacaaaaaggaggaggaagatgacggact 
               
               
                   
               
               
                 ggtggagtttgtgcgcgagttcgccccccggcggcgcgtgcagtggcgcgggcggaaagtgaaac 
               
               
                   
               
               
                 cggtgctgcggcccggcaccacggtggtcttcacgcccggcgagcgttccggctccgcctccaag 
               
               
                   
               
               
                 cgctcctacgacgaggtgtacggggacgaggacatcctcgagcaggcggtcgagcgtctgggcga 
               
               
                   
               
               
                 gtttgcgtacggcaagcgcagccgccccgcgcccttgaaagaggaggcggtgtccatcccgctgg 
               
               
                   
               
               
                 accacggcaaccccacgccgagcctgaagccggtgaccctgcagcaggtgctaccgagcgcggcg 
               
               
                   
               
               
                 ccgcgccggggcttcaagcgcgagggcggcgaggatctgtacccgaccatgcagctgatggtgcc 
               
               
                   
               
               
                 caagcgccagaagctggaggacgtgctggagcacatgaaggtggaccccgaggtgcagcccgagg 
               
               
                   
               
               
                 tcaaggtgcggcccatcaagcaggtggccccgggcctgggcgtgcagaccgtggacatcaagatc 
               
               
                   
               
               
                 cccacggagcccatggaaacgcagaccgagcccgtgaagcccagcaccagcaccatggaggtgca 
               
               
                   
               
               
                 gacggatccctggatgccagcaccagcttccaccagcactcgccgaagacgcaagtacggcgcgg 
               
               
                   
               
               
                 ccagcctgctgatgcccaactacgcgctgcatccttccatcatccccacgccgggctaccgcggc 
               
               
                   
               
               
                 acgcgcttctaccgcggctacaccagcagccgccgccgcaagaccaccacccgccgccgtcgtcg 
               
               
                   
               
               
                 cagccgccgcagcagcaccgcgacttccgccttggtgcggagagtgtatcgcagcgggcgcgagc 
               
               
                   
               
               
                 ctctgaccctgccgcgcgcgcgctaccacccgagcatcgccatttaactaccgcctcctacttgc 
               
               
                   
               
               
                 agatatggccctcacatgccgcctccgcgtccccattacgggctaccgaggaagaaagccgcgcc 
               
               
                   
               
               
                 gtagaaggctgacggggaacgggctgcgtcgccatcaccaccggcggcggcgcgccatcagcaag 
               
               
                   
               
               
                 cggttggggggaggcttcctgcccgcgctgatccccatcatcgccgcggcgatcggggcgatccc 
               
               
                   
               
               
                 cggcatagcttccgtggcggtgcaggcctctcagcgccactgagacacaaaaaagcatggatttg 
               
               
                   
               
               
                 taataaaaaaaaaaatggactgacgctcctggtcctgtgatgtgtgtttttagatggaagacatc 
               
               
                   
               
               
                 aatttttcgtccctggcaccgcgacacggcacgcggccgtttatgggcacctggagcgacatcgg 
               
               
                   
               
               
                 caacagccaactgaacgggggcgccttcaattggagcagtctctggagcgggcttaagaatttcg 
               
               
                   
               
               
                 ggtccacgctcaaaacctatggcaacaaggcgtggaacagcagcacagggcaggcgctgagggaa 
               
               
                   
               
               
                 aagctgaaagaacagaacttccagcagaaggtggttgatggcctggcctcaggcatcaacggggt 
               
               
                   
               
               
                 ggttgacctggccaaccaggccgtgcagaaacagatcaacagccgcctggacgcggtcccgcccg 
               
               
                   
               
               
                 cggggtccgtggagatgccccaggtggaggaggagctgcctcccctggacaagcgcggcgacaag 
               
               
                   
               
               
                 cgaccgcgtcccgacgcggaggagacgctgctgacgcacacggacgagccgcccccgtacgagga 
               
               
                   
               
               
                 ggcggtgaaactgggcctgcccaccacgcggcccgtggcgcctctggccaccggagtgctgaaac 
               
               
                   
               
               
                 ccagcagcagccagcccgcgaccctggacttgcctccgcctcgcccctccacagtggctaagccc 
               
               
                   
               
               
                 ctgccgccggtggccgtcgcgtcgcgcgccccccgaggccgcccccaggcgaactggcagagcac 
               
               
                   
               
               
                 tctgaacagcatcgtgggtctgggagtgcagagtgtgaagcgccgccgctgctattaaaagacac 
               
               
                   
               
               
                 tgtagcgcttaacttgcttgtctgtgtgtatatgtatgtccgccgaccagaaggaggagtgtgaa 
               
               
                   
               
               
                 gaggcgcgtcgccgagttgcaagatggccaccccatcgatgctgccccagtgggcgtacatgcac 
               
               
                   
               
               
                 atcgccggacaggacgcttcggagtacctgagtccgggtctggtgcagttcgcccgcgccacaga 
               
               
                   
               
               
                 cacctacttcagtctggggaacaagtttaggaaccccacggtggcgcccacgcacgatgtgacca 
               
               
                   
               
               
                 ccgaccgcagccagcggctgacgctgcgcttcgtgcccgtggaccgcgaggacaacacctactcg 
               
               
                   
               
               
                 tacaaagtgcgctacacgctggccgtgggcgacaaccgcgtgctggacatggccagcacctactt 
               
               
                   
               
               
                 tgacatccgcggcgtgctggaccggggccctagcttcaaaccctactctggcaccgcctacaaca 
               
               
                   
               
               
                 gcctagctcccaagggagctcccaattccagccagtgggagcaagcaaaaacaggcaatggggga 
               
               
                   
               
               
                 actatggaaacacacacatatggtgtggccccaatgggcggagagaatattacaaaagatggtct 
               
               
                   
               
               
                 tcaaattggaactgacgttacagcgaatcagaataaaccaatttatgccgacaaaacatttcaac 
               
               
                   
               
               
                 cagaaccgcaagtaggagaagaaaattggcaagaaactgaaaacttttatggcggtagagctctt 
               
               
                   
               
               
                 aaaaaagacacaaacatgaaaccttgctatggctcctatgctagacccaccaatgaaaaaggagg 
               
               
                   
               
               
                 tcaagctaaacttaaagttggagatgatggagttccaaccaaagaattcgacatagacctggctt 
               
               
                   
               
               
                 tctttgatactcccggtggcaccgtgaacggtcaagacgagtataaagcagacattgtcatgtat 
               
               
                   
               
               
                 accgaaaacacgtatttggaaactccagacacgcatgtggtatacaaaccaggcaaggatgatgc 
               
               
                   
               
               
                 aagttctgaaattaacctggttcagcagtctatgcccaacagacccaactacattgggttcaggg 
               
               
                   
               
               
                 acaactttatcggtcttatgtactacaacagcactggcaatatgggtgtgcttgctggtcaggcc 
               
               
                   
               
               
                 tcccagctgaatgctgtggttgatttgcaagacagaaacaccgagctgtcctaccagctcttgct 
               
               
                   
               
               
                 tgactctttgggtgacagaacccggtatttcagtatgtggaaccaggcggtggacagttatgacc 
               
               
                   
               
               
                 ccgatgtgcgcatcatcgaaaaccatggtgtggaggatgaattgccaaactattgcttccccttg 
               
               
                   
               
               
                 gacggctctggcactaacgccgcataccaaggtgtgaaagtaaaagatggtcaagatggtgatgt 
               
               
                   
               
               
                 tgagagtgaatgggaaaatgacgatactgttgcagctcgaaatcaattatgtaaaggtaacattt 
               
               
                   
               
               
                 tcgccatggagattaatctccaggctaacctgtggagaagtttcctctactcgaacgtggccctg 
               
               
                   
               
               
                 tacctgcccgactcctacaagtacacgccgaccaacgtcacgctgccgaccaacaccaacaccta 
               
               
                   
               
               
                 cgattacatgaatggcagagtgacacctccctcgctggtagacgcctacctcaacatcggggcgc 
               
               
                   
               
               
                 gctggtcgctggaccccatggacaacgtcaaccccttcaaccaccaccgcaacgcgggcctgcgc 
               
               
                   
               
               
                 taccgctccatgctcctgggcaacgggcgctacgtgcccttccacatccaggtgccccaaaagtt 
               
               
                   
               
               
                 tttcgccatcaagagcctcctgctcctgcccgggtcctacacctacgagtggaacttccgcaagg 
               
               
                   
               
               
                 acgtcaacatgatcctgcagagctccctaggcaacgacctgcgcacggacggggcctccatcgcc 
               
               
                   
               
               
                 ttcaccagcatcaacctctacgccaccttcttccccatggcgcacaacaccgcctccacgctcga 
               
               
                   
               
               
                 ggccatgctgcgcaacgacaccaacgaccagtccttcaacgactacctctcggcggccaacatgc 
               
               
                   
               
               
                 tctaccccatcccggccaacgccaccaacgtgcccatctccatcccctcgcgcaactgggccgcc 
               
               
                   
               
               
                 ttccgcggatggtccttcacgcgcctgaagacccgcgagacgccctcgctcggctccgggttcga 
               
               
                   
               
               
                 cccctacttcgtctactcgggctccatcccctacctagacggcaccttctacctcaaccacacct 
               
               
                   
               
               
                 tcaagaaggtctccatcaccttcgactcctccgtcagctggcccggcaacgaccgcctcctgacg 
               
               
                   
               
               
                 cccaacgagttcgaaatcaagcgcaccgtcgacggagagggatacaacgtggcccagtgcaacat 
               
               
                   
               
               
                 gaccaaggactggttcctggtccagatgctggcccactacaacatcggctaccagggcttctacg 
               
               
                   
               
               
                 tgcccgagggctacaaggaccgcatgtactccttcttccgcaacttccagcccatgagccgccag 
               
               
                   
               
               
                 gtcgtggacgaggtcaactacaaggactaccaggccgtcaccctggcctaccagcacaacaactc 
               
               
                   
               
               
                 gggcttcgtcggctacctcgcgcccaccatgcgccagggccagccctaccccgccaactacccct 
               
               
                   
               
               
                 acccgctcatcggcaagagcgccgtcgccagcgtcacccagaaaaagttcctctgcgaccgggtc 
               
               
                   
               
               
                 atgtggcgcatccccttctccagcaacttcatgtccatgggcgcgctcaccgacctcggccagaa 
               
               
                   
               
               
                 catgctctacgccaactccgcccacgcgctagacatgaatttcgaagtcgaccccatggatgagt 
               
               
                   
               
               
                 ccacccttctctatgttgtcttcgaagtcttcgacgtcgtccgagtgcaccagccccaccgcggc 
               
               
                   
               
               
                 gtcatcgaagccgtctacctgcgcacgcccttctcggccggcaacgccaccacctaagccgctct 
               
               
                   
               
               
                 tgcttcttgcaagatgacggcgggctccggcgagcaggagctcagggccatcctccgcgacctgg 
               
               
                   
               
               
                 gctgcgggccctgcttcctgggcaccttcgacaagcgcttccctggattcatggccccgcacaag 
               
               
                   
               
               
                 ctggcctgcgccatcgtgaacacggccggccgcgagaccgggggcgagcactggctggccttcgc 
               
               
                   
               
               
                 ctggaacccgcgctcccacacatgctacctcttcgaccccttcgggttctcggacgagcgcctca 
               
               
                   
               
               
                 agcagatctaccagttcgagtacgagggcctgctgcgtcgcagcgccctggccaccgaggaccgc 
               
               
                   
               
               
                 tgcgtcaccctggaaaagtccacccagaccgtgcagggtccgcgctcggccgcctgcgggctctt 
               
               
                   
               
               
                 ctgctgcatgttcctgcacgccttcgtgcactggcccgaccgccccatggacaagaaccccacca 
               
               
                   
               
               
                 tgaacttactgacgggggtgcccaacggcatgctccagtcgccccaggtggaacccaccctgcgc 
               
               
                   
               
               
                 cgcaaccaggaagcgctctaccgcttcctcaatgcccactccgcctactttcgctcccaccgcgc 
               
               
                   
               
               
                 gcgcatcgagaaggccaccgccttcgaccgcatgaatcaagacatgtaaaaaaccggtgtgtgta 
               
               
                   
               
               
                 tgtgaatgctttattcataataaacagcacatgtttatgccaccttctctgaggctctgacttta 
               
               
                   
               
               
                 tttagaaatcgaaggggttctgccggctctcggcatggcccgcgggcagggatacgttgcggaac 
               
               
                   
               
               
                 tggtacttgggcagccacttgaactcggggatcagcagcttgggcacggggaggtcggggaacga 
               
               
                   
               
               
                 gtcgctccacagcttgcgcgtgagttgcagggcgcccagcaggtcgggcgcggagatcttgaaat 
               
               
                   
               
               
                 cgcagttgggacccgcgttctgcgcgcgagagttgcggtacacggggttgcagcactggaacacc 
               
               
                   
               
               
                 atcagggccgggtgcttcacgcttgccagcaccgtcgcgtcggtgatgccctccacgtccagatc 
               
               
                   
               
               
                 ctcggcgttggccatcccgaagggggtcatcttgcaggtctgccgccccatgctgggcacgcagc 
               
               
                   
               
               
                 cgggcttgtggttgcaatcgcagtgcagggggatcagcatcatctgggcctgctcggagctcatg 
               
               
                   
               
               
                 cccgggtacatggccttcatgaaagcctccagctggcggaaggcctgctgcgccttgccgccctc 
               
               
                   
               
               
                 ggtgaagaagaccccgcaggacttgctagagaactggttggtggcgcagccggcgtcgtgcacgc 
               
               
                   
               
               
                 agcagcgcgcgtcgttgttggccagctgcaccacgctgcgcccccagcggttctgggtgatcttg 
               
               
                   
               
               
                 gcccggttggggttctccttcagcgcgcgctgcccgttctcgctcgccacatccatctcgatagt 
               
               
                   
               
               
                 gtgctccttctggatcatcacggtcccgtgcaggcaccgcagcttgccctcggcttcggtgcagc 
               
               
                   
               
               
                 cgtgcagccacagcgcgcagccggtgcactcccagttcttgtgggcgatctgggagtgcgagtgc 
               
               
                   
               
               
                 acgaagccctgcaggaagcggcccatcatcgcggtcagggtcttgttgctggtgaaggtcagcgg 
               
               
                   
               
               
                 gatgccgcggtgctcctcgttcacatacaggtggcagatgcggcggtacacctcgccctgctcgg 
               
               
                   
               
               
                 gcatcagctggaaggcggacttcaggtcgctctccacgcggtaccggtccatcagcagcgtcatc 
               
               
                   
               
               
                 acttccatgcccttctcccaggccgaaacgatcggcaggctcagggggttcttcaccgccattgt 
               
               
                   
               
               
                 catcttagtcgccgccgccgaggtcagggggtcgttctcgtccagggtctcaaacactcgcttgc 
               
               
                   
               
               
                 cgtccttctcgatgatgcgcacggggggaaagctgaagcccacggccgccagctcctcctcggcc 
               
               
                   
               
               
                 tgcctttcgtcctcgctgtcctggctgatgtcttgcaaaggcacatgcttggtcttgcggggttt 
               
               
                   
               
               
                 ctttttgggcggcagaggcggcggcgatgtgctgggagagcgcgagttctcgttcaccacgacta 
               
               
                   
               
               
                 tttcttcttcttggccgtcgtccgagaccacgcggcggtaggcatgcctcttctggggcagaggc 
               
               
                   
               
               
                 ggaggcgacgggctctcgcggttcggcgggcggctggcagagccccttccgcgttcgggggtgcg 
               
               
                   
               
               
                 ctcctggcggcgctgctctgactgacttcctccgcggccggccattgtgttctcctagggagcaa 
               
               
                   
               
               
                 caacaagcatggagactcagccatcgtcgccaacatcgccatctgcccccgccgccaccgccgac 
               
               
                   
               
               
                 gagaaccagcagcagaatgaaagcttaaccgccccgccgcccagccccacctccgacgccgcggc 
               
               
                   
               
               
                 cccagacatgcaagagatggaggaatccatcgagattgacctgggctacgtgacgcccgcggagc 
               
               
                   
               
               
                 acgaggaggagctggcagcgcgcttttcagccccggaagagaaccaccaagagcagccagagcag 
               
               
                   
               
               
                 gaagcagagaacgagcagaaccaggctgggcacgagcatggcgactacctgagcggggcagagga 
               
               
                   
               
               
                 cgtgctcatcaagcatctggcccgccaatgcatcatcgtcaaggacgcgctgctcgaccgcgccg 
               
               
                   
               
               
                 aggtgcccctcagcgtggcggagctcagccgcgcctacgagcgcaacctcttctcgccgcgcgtg 
               
               
                   
               
               
                 ccccccaagcgccagcccaacggcacctgtgagcccaacccgcgcctcaacttctacccggtctt 
               
               
                   
               
               
                 cgcggtgcccgaggccctggccacctaccacctctttttcaagaaccaaaggatccccgtctcct 
               
               
                   
               
               
                 gccgcgccaaccgcacccgcgccgacgccctgctcaacctgggccccggcgcccgcctacctgat 
               
               
                   
               
               
                 atcacctccttggaagaggttcccaagatcttcgagggtctgggcagcgacgagactcgggccgc 
               
               
                   
               
               
                 gaacgctctgcaaggaagcggagaggagcatgagcaccacagcgccctggtggagttggaaggcg 
               
               
                   
               
               
                 acaacgcgcgcctggcggtcctcaagcgcacggtcgagctgacccacttcgcctacccggcgctc 
               
               
                   
               
               
                 aacctgccccccaaggtcatgagcgccgtcatggaccaggtgctcatcaagcgcgcctcgcccct 
               
               
                   
               
               
                 ctcggaggaggagatgcaggaccccgagagttcggacgagggcaagcccgtggtcagcgacgagc 
               
               
                   
               
               
                 agctggcgcgctggctgggagcgagtagcaccccccagagcctggaagagcggcgcaagctcatg 
               
               
                   
               
               
                 atggccgtggtcctggtgaccgtggagctggagtgtctgcgccgcttctttgccgacgcggagac 
               
               
                   
               
               
                 cctgcgcaaggtcgaggagaacctgcactacctcttcaggcacgggttcgtgcgccaggcctgca 
               
               
                   
               
               
                 agatctccaacgtggagctgaccaacctggtctcctacatgggcatcctgcacgagaaccgcctg 
               
               
                   
               
               
                 gggcaaaacgtgctgcacaccaccctgcgcggggaggcccgccgcgactacatccgcgactgcgt 
               
               
                   
               
               
                 ctacctgtacctctgccacacctggcagacgggcatgggcgtgtggcagcagtgcctggaggagc 
               
               
                   
               
               
                 agaacctgaaagagctctgcaagctcctgcagaagaacctcaaggccctgtggaccgggttcgac 
               
               
                   
               
               
                 gagcgtaccaccgcctcggacctggccgacctcatcttccccgagcgcctgcggctgacgctgcg 
               
               
                   
               
               
                 caacgggctgcccgactttatgagccaaagcatgttgcaaaactttcgctctttcatcctcgaac 
               
               
                   
               
               
                 gctccgggatcctgcccgccacctgctccgcgctgccctcggacttcgtgccgctgaccttccgc 
               
               
                   
               
               
                 gagtgccccccgccgctctggagccactgctacttgctgcgcctggccaactacctggcctacca 
               
               
                   
               
               
                 ctcggacgtgatcgaggacgtcagcggcgagggtctgctggagtgccactgccgctgcaacctct 
               
               
                   
               
               
                 gcacgccgcaccgctccctggcctgcaacccccagctgctgagcgagacccagatcatcggcacc 
               
               
                   
               
               
                 ttcgagttgcaaggccccggcgacggcgagggcaaggggggtctgaaactcaccccggggctgtg 
               
               
                   
               
               
                 gacctcggcctacttgcgcaagttcgtgcccgaggactaccatcccttcgagatcaggttctacg 
               
               
                   
               
               
                 aggaccaatcccagccgcccaaggccgagctgtcggcctgcgtcatcacccagggggccatcctg 
               
               
                   
               
               
                 gcccaattgcaagccatccagaaatcccgccaagaatttctgctgaaaaagggccacggggtcta 
               
               
                   
               
               
                 cttggacccccagaccggagaggagctcaaccccagcttcccccaggatgccccgaggaagcagc 
               
               
                   
               
               
                 aagaagctgaaagtggagctgccgccgccggaggatttggaggaagactgggagagcagtcaggc 
               
               
                   
               
               
                 agaggaggaggagatggaagactgggacagcactcaggcagaggaggacagcctgcaagacagtc 
               
               
                   
               
               
                 tggaggaggaagacgaggtggaggaggcagaggaagaagcagccgccgccagaccgtcgtcctcg 
               
               
                   
               
               
                 gcggagaaagcaagcagcacggataccatctccgctccgggtcggggtcgcggcggccgggccca 
               
               
                   
               
               
                 cagtaggtgggacgagaccgggcgcttcccgaaccccaccacccagaccggtaagaaggagcggc 
               
               
                   
               
               
                 agggatacaagtcctggcgggggcacaaaaacgccatcgtctcctgcttgcaagcctgcgggggc 
               
               
                   
               
               
                 aacatctccttcacccggcgctacctgctcttccaccgcggggtgaacttcccccgcaacatctt 
               
               
                   
               
               
                 gcattactaccgtcacctccacagcccctactactgtttccaagaagaggcagaaacccagcagc 
               
               
                   
               
               
                 agcagaaaaccagcggcagcagcagctagaaaatccacagcggcggcaggtggactgaggatcgc 
               
               
                   
               
               
                 ggcgaacgagccggcgcagacccgggagctgaggaaccggatctttcccaccctctatgccatct 
               
               
                   
               
               
                 tccagcagagtcgggggcaggagcaggaactgaaagtcaagaaccgttctctgcgctcgctcacc 
               
               
                   
               
               
                 cgcagttgtctgtatcacaagagcgaagaccaacttcagcgcactctcgaggacgccgaggctct 
               
               
                   
               
               
                 cttcaacaagtactgcgcgctcactcttaaagagtagcccgcgcccgcccacacacggaaaaagg 
               
               
                   
               
               
                 cgggaattacgtcaccacctgcgcccttcgcccgaccatcatgagcaaagagattcccacgcctt 
               
               
                   
               
               
                 acatgtggagctaccagccccagatgggcctggccgccggcgccgcccaggactactccacccgc 
               
               
                   
               
               
                 atgaactggctcagtgccgggcccgcgatgatctcacgggtgaatgacatccgcgcccaccgaaa 
               
               
                   
               
               
                 ccagatactcctagaacagtcagcgatcaccgccacgccccgccatcaccttaatccgcgtaatt 
               
               
                   
               
               
                 ggcccgccgccctggtgtaccaggaaattccccagcccacgaccgtactacttccgcgagacgcc 
               
               
                   
               
               
                 caggccgaagtccagctgactaactcaggtgtccagctggccggcggcgccgccctgtgtcgtca 
               
               
                   
               
               
                 ccgccccgctcagggtataaagcggctggtgatccgaggcagaggcacacagctcaacgacgagg 
               
               
                   
               
               
                 tggtgagctcttcgctgggtctgcgacctgacggagtcttccaactcgccggatcggggagatct 
               
               
                   
               
               
                 tccttcacgcctcgtcaggccgtcctgactttggagagttcgtcctcgcagccccgctcgggcgg 
               
               
                   
               
               
                 catcggcactctccagttcgtggaggagttcactccctcggtctacttcaaccccttctccggct 
               
               
                   
               
               
                 cccccggccactacccggacgagttcatcccgaacttcgacgccatcagcgagtcggtggacggc 
               
               
                   
               
               
                 tacgattgaatgtcccatggtggcgcagctgacctagctcggcttcgacacctggaccactgccg 
               
               
                   
               
               
                 ccgcttccgctgcttcgctcgggatctcgccgagtttgcctactttgagctgcccgaggagcacc 
               
               
                   
               
               
                 ctcagggcccagcccacggagtgcggatcatcgtcgaagggggcctcgactcccacctgcttcgg 
               
               
                   
               
               
                 atcttcagccagcgaccgatcctggtcgagcgcgaacaaggacagacccttcttactttgtactg 
               
               
                   
               
               
                 catctgcaaccaccccggcctgcatgaaagtctttgttgtctgctgtgtactgagtataataaaa 
               
               
                   
               
               
                 gctgagatcagcgactactccggactcgattgtggtgttcctgctatcaaccggtccctgttctt 
               
               
                   
               
               
                 caccgggaacgagaccgagctccagctccagtgtaagccccacaagaagtacctcacctggctgt 
               
               
                   
               
               
                 tccagggctccccgatcgccgttgtcaaccactgcgacaacgacggagtcctgctgagcggccct 
               
               
                   
               
               
                 gccaaccttactttttccacccgcagaagcaagctccagctcttccaacccttcctccccgggac 
               
               
                   
               
               
                 ctatcagtgcgtctcaggaccctgccatcacaccttccacctgatcccgaataccacagcgccgc 
               
               
                   
               
               
                 tccccgctactaacaaccaaactacccaccaacgccaccgtcgcgacctttcctctgaatctaat 
               
               
                   
               
               
                 accactaccggaggtggcttctgctgttagtgctcccccgtcccgtcgacccccggtcccccact 
               
               
                   
               
               
                 cagtcccccgaggaggttcgcaaatgcaaattccaagaaccctggaaattcctcaaatgctaccg 
               
               
                   
               
               
                 ccaaaaatcagacatgcatcccagctggatcatgatcattgggatcgtgaacattctggcctgca 
               
               
                   
               
               
                 ccctcatctcctttgtgatttacccctgctttgactttggttggaactcgccagaggcgctctat 
               
               
                   
               
               
                 ctcccgcctgaacctgacacaccaccacagcagcaacctcaggcacacgcactaccaccaccaca 
               
               
                   
               
               
                 gcctaggccacaatacatgcccatattagactatgaggccgagccacagcgacccatgctccccg 
               
               
                   
               
               
                 ctattagttacttcaatctaaccggcggagatgactgacccactggccaataacaacgtcaacga 
               
               
                   
               
               
                 ccttctcctggacatggacggccgcgcctcggagcagcgactcgcccaacttcgcattcgtcagc 
               
               
                   
               
               
                 agcaggagagagccgtcaaggagctgcaggacggcatagccatccaccagtgcaagagaggcatc 
               
               
                   
               
               
                 ttctgcctggtgaaacaggccaagatctcctacgaggtcacccagaccgaccatcgcctctccta 
               
               
                   
               
               
                 cgagctcctgcagcagcgccagaagttcacctgcctggtcggagtcaaccccatcgtcatcaccc 
               
               
                   
               
               
                 agcagtcgggcgataccaaggggtgcatccactgctcctgcgactcccccgactgcgtccacact 
               
               
                   
               
               
                 ctgatcaagaccctctgcggcctccgcgacctcctccccatgaactaatcacccccttatccagt 
               
               
                   
               
               
                 gaaataaagatcatattgatgatgatttaaataaaaaaaataatcatttgatttgaaataaagat 
               
               
                   
               
               
                 acaatcatattgatgatttgagtttaacaaaaataaagaatcacttacttgaaatctgataccag 
               
               
                   
               
               
                 gtctctgtccatgttttctgccaacaccacctcactcccctcttcccagctctggtactgcaggc 
               
               
                   
               
               
                 cccggcgggctgcaaacttcctccacacgctgaaggggatgtcaaattcctcctgtccctcaatc 
               
               
                   
               
               
                 ttcattttatcttctatcagatgtccaaaaagcgcgtccgggtggatgatgacttcgaccccgtc 
               
               
                   
               
               
                 tacccctacgatgcagacaacgcaccgaccgtgcccttcatcaacccccccttcgtctcttcaga 
               
               
                   
               
               
                 tggattccaagagaagcccctgggggtgttgtccctgcgactggctgaccccgtcaccaccaaga 
               
               
                   
               
               
                 acggggaaatcaccctcaagctgggagagggggtggacctcgactcgtcgggaaaactcatctcc 
               
               
                   
               
               
                 aacacggccaccaaggccgccgcccctctcagtatttcaaacaacaccatttcccttaaaactgc 
               
               
                   
               
               
                 tgcccctttctacaacaacaatggaactttaagcctcaatgtctccacaccattagcagtatttc 
               
               
                   
               
               
                 ccacatttaacactttaggcataagtcttggaaacggtcttcagacttcaaataagttgttgact 
               
               
                   
               
               
                 gtacaactaactcatcctcttacattcagctcaaatagcatcacagtaaaaacagacaaagggct 
               
               
                   
               
               
                 atatattaactccagtggaaacagaggacttgaggctaatataagcctaaaaagaggactagttt 
               
               
                   
               
               
                 ttgacggtaatgctattgcaacatatattggaaatggcttagactatggatcttatgatagtgat 
               
               
                   
               
               
                 ggaaaaacaagacccgtaattaccaaaattggagcaggattaaattttgatgctaacaaagcaat 
               
               
                   
               
               
                 agctgtcaaactaggcacaggtttaagttttgactccgctggtgccttgacagctggaaacaaac 
               
               
                   
               
               
                 aggatgacaagctaacactttggactacccctgacccaagccctaattgtcaattactttcagac 
               
               
                   
               
               
                 agagatgccaaatttactctctgtcttacaaaatgcggtagtcaaatactaggcactgtggcagt 
               
               
                   
               
               
                 ggcggctgttactgtaggatcagcactaaatccaattaatgacacagtcaaaagcgccatagttt 
               
               
                   
               
               
                 tccttagatttgattccgatggtgtactcatgtcaaactcatcaatggtaggtgattactggaac 
               
               
                   
               
               
                 tttagggagggacagaccactcaaagtgtagcctatacaaatgctgtgggattcatgccaaatat 
               
               
                   
               
               
                 aggtgcatatccaaaaacccaaagtaaaacacctaaaaatagcatagtcagtcaggtatatttaa 
               
               
                   
               
               
                 ctggagaaactactatgccaatgacactaaccataactttcaatggcactgatgaaaaagacaca 
               
               
                   
               
               
                 accccagttagcacctactctatgacttttacatggcagtggactggagactataaggacaaaaa 
               
               
                   
               
               
                 tattacctttgctaccaactcattctctttttcctacatcgcccaggaataatcccacccagcaa 
               
               
                   
               
               
                 gccaaccccttttcccaccacctttgtctatatggaaactctgaaacagaaaaataaagttcaag 
               
               
                   
               
               
                 tgttttattgaatcaacagttttacaggactcgagcagttatttttcctccaccctcccaggaca 
               
               
                   
               
               
                 tggaatacaccaccctctccccccgcacagccttgaacatctgaatgccattggtgatggacatg 
               
               
                   
               
               
                 cttttggtctccacgttccacacagtttcagagcgagccagtctcggatcggtcagggagatgaa 
               
               
                   
               
               
                 accctccgggcactcccgcatctgcacctcacagctcaacagctgaggattgtcctcggtggtcg 
               
               
                   
               
               
                 ggatcacggttatctggaagaagcagaagagcggcggtgggaatcatagtccgcgaacgggatcg 
               
               
                   
               
               
                 gccggtggIgtcgcatcaggccccgcagcagtcgctgccgccgccgctccgtcaagctgctgctcagggggttc 
               
               
                   
               
               
                 gggtccagggactccctcagcatgatgcccacggccctcagcatcagtcgtctggtgcggcgggc 
               
               
                   
               
               
                 gcagcagcgcatgcgaatctcgctcaggtcactgcagtacgtgcaacacaggaccaccaggttgt 
               
               
                   
               
               
                 tcaacagtccatagttcaacacgctccagccgaaactcatcgcgggaaggatgctacccacgtgg 
               
               
                   
               
               
                 ccgtcgtaccagatcctcaggtaaatcaagtggcgctccctccagaagacgctgcccatgtacat 
               
               
                   
               
               
                 gatctccttgggcatgtggcggttcaccacctcccggtaccacatcaccctctggttgaacatgc 
               
               
                   
               
               
                 agccccggatgatcctgcggaaccacagggccagcaccgccccgcccgccatgcagcgaagagac 
               
               
                   
               
               
                 cccggatcccggcaatgacaatggaggacccaccgctcgtacccgtggatcatctgggagctgaa 
               
               
                   
               
               
                 caagtctatgttggcacagcacaggcatatgctcatgcatctcttcagcactctcagctcctcgg 
               
               
                   
               
               
                 gggtcaaaaccatatcccagggcacggggaactcttgcaggacagcgaaccccgcagaacagggc 
               
               
                   
               
               
                 aatcctcgcacataacttacattgtgcatggacagggtatcgcaatcaggcagcaccgggtgatc 
               
               
                   
               
               
                 ctccaccagagaagcgcgggtctcggtctcctcacagcgtggtaagggggccggccgatacgggt 
               
               
                   
               
               
                 gatggcgggacgcggctgatcgtgttctcgaccgtgtcatgatgcagttgctttcggacattttc 
               
               
                   
               
               
                 gtacttgctgtagcagaacctggtccgggcgctgcacaccgatcgccggcggcggtctcggcgct 
               
               
                   
               
               
                 tggaacgctcggtgttaaagttgtaaaacagccactctctcagaccgtgcagcagatctagggcc 
               
               
                   
               
               
                 tcaggagtgatgaagatcccatcatgcctgatagctctgatcacatcgaccaccgtggaatgggc 
               
               
                   
               
               
                 caggcccagccagatgatgcaattttgttgggtttcggtgacggcgggggagggaagaacaggaa 
               
               
                   
               
               
                 gaaccatgattaacttttaatccaaacggtctcggagcacttcaaaatgaaggtcacggagatgg 
               
               
                   
               
               
                 cacctctcgcccccgctgtgttggtggaaaataacagccaggtcaaaggtgatacggttctcgag 
               
               
                   
               
               
                 atgttccacggtggcttccagcaaagcctccacgcgcacatccagaaacaagacaatagcgaaag 
               
               
                   
               
               
                 cgggagggttctctaattcctcaaccatcatgttacactcctgcaccatccccagataattttca 
               
               
                   
               
               
                 tttttccagccttgaatgattcgaactagttcctgaggtaaatccaagccagccatgataaaaag 
               
               
                   
               
               
                 ctcgcgcagagcaccctccaccggcattcttaagcacaccctcataattccaagatattctgctc 
               
               
                   
               
               
                 ctggttcacctgcagcagattgacaagcggaatatcaaaatctctgccgcgatccctgagctcct 
               
               
                   
               
               
                 ccctcagcaataactgtaagtactctttcatatcgtctccgaaatttttagccataggaccccca 
               
               
                   
               
               
                 ggaataagagaagggcaagccacattacagataaaccgaagtcccccccagtgagcattgccaaa 
               
               
                   
               
               
                 tgtaagattgaaataagcatgctggctagacccggtgatatcttccagataactggacagaaaat 
               
               
                   
               
               
                 cgggtaagcaatttttaagaaaatcaacaaaagaaaaatcttccaggtgcacgtttagggcctcg 
               
               
                   
               
               
                 ggaacaacgatggagtaagtgcaagggcgttctctccagcaccaggcaggccacggggtctccgg 
               
               
                   
               
               
                 cgcgaccctcgtaaaaattgtcgctatgattgaaaaccatcacagagagacgttcccggtggccg 
               
               
                   
               
               
                 gcgtgaatgattcgagaagaagcatacacccccggaacattggagtccgtgagtgaaaaaaagcg 
               
               
                   
               
               
                 gccgaggaagcaatgaggcactacaacgctcactctcaagtccagcaaagcgatgccatgcggat 
               
               
                   
               
               
                 gaagcacaaaattttcaggtgcgtaaaaaatgtaattactcccctcctgcacaggcagcgaagct 
               
               
                   
               
               
                 cccgatccctccagatacacatacaaagcctcagcgtccatagcttaccgagcggcagcagcagc 
               
               
                   
               
               
                 ggcacacaacaggcgcaagagtcagagaaaagactgagctctaacctgtccgcccgctctctgct 
               
               
                   
               
               
                 caatatatagccccagatctacactgacgtaaaggccaaagtctaaaaatacccgccaaataatc 
               
               
                   
               
               
                 acacacgcccagcacacgcccagaaaccggtgacacactcagaaaaatacgcgcacttcctcaaa 
               
               
                   
               
               
                 cggccaaactgccgtcatttccgggttcccacgctacgtcatcaaaacacgactttcaaattccg 
               
               
                   
               
               
                 tcgaccgttaaaaacatcacccgccccgcccctaacggtcgccgctcccgcagccaatcaccttc 
               
               
                   
               
               
                 ctccctccccaaattcaaacagctcatttgcatattaacgcgcaccaaaagtttgaggtatatta 
               
               
                   
               
               
                 Ttgatgatg 
               
               
                   
               
               
                 2, C7010CMV-HIVgp140 AE1. 
               
               
                 SEQ ID NO: 7 
                   
               
               
                 catcatcaataatatacctcaaacttttggtgcgcgttaatatgcaaatgagctgtttgaatttg 
                   
               
               
                   
               
               
                 gggagggaggaaggtgattggccgagagacgggcgaccgttaggggcggggcgggtgacgttttg 
               
               
                   
               
               
                 atgacgtggccgtgaggcggagccggtttgcaagttctcgtgggaaaagtgacgtcaaacgaggt 
               
               
                   
               
               
                 gtggtttgaacacggaaatactcaattttcccgcgctctctgacaggaaatgaggtgtttctggg 
               
               
                   
               
               
                 cggatgcaagtgaaaacgggccattttcgcgcgaaaactgaatgaggaagtgaaaatctgagtaa 
               
               
                   
               
               
                 tttcgcgtttatggcagggaggagtatttgccgagggccgagtagactttgaccgattacgtggg 
               
               
                   
               
               
                 ggtttcgattaccgtatttttcacctaaatttccgcgtacggtgtcaaagtccggtgtttttacg 
               
               
                   
               
               
                 tacgatatcatttccccgaaagtgccacctgaccgtaactataacggtcctaaggtagcgaaagc 
               
               
                   
               
               
                 tcagatctcccgatcccctatggtgcactctcagtacaatctgctctgatgccgcatagttaagc 
               
               
                   
               
               
                 cagtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctac 
               
               
                   
               
               
                 aacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgttttgcgctgc 
               
               
                   
               
               
                 ttcgcgatgtacgggccagatatacgcgttgacattgattattgactagttattaatagtaatca 
               
               
                   
               
               
                 attacggggtcattagttcatagcccatatatggagttccgcgttacataacttacggtaaatgg 
               
               
                   
               
               
                 cccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgacgtatgttcccatag 
               
               
                   
               
               
                 taacgccaatagggactttccattgacgtcaatgggtggagtatttacggtaaactgcccacttg 
               
               
                   
               
               
                 gcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcc 
               
               
                   
               
               
                 cgcctggcattatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtat 
               
               
                   
               
               
                 tagtcatcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggttt 
               
               
                   
               
               
                 gactcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaa 
               
               
                   
               
               
                 tcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtg 
               
               
                   
               
               
                 tacggtgggaggtctatataagcagagctcgtttagtgaaccgtcagatcactagaagctttatt 
               
               
                   
               
               
                 gcggtagtttatcacagttaaattgctaacgcagtcagtgcttctgacacaacagtctcgaactt 
               
               
                   
               
               
                 aagctgcagaagttggtcgtgaggcactgggcaggtaagtatcaaggttacaagacaggtttaag 
               
               
                   
               
               
                 gagaccaatagaaactgggcttgtcgagacagagaagactcttgcgtttctgataggcacctatt 
               
               
                   
               
               
                 ggtcttactgacatccactttgcctttctctccacaggtgtccactcccagttcaattacagctc 
               
               
                   
               
               
                 ttaaaaggctagagtacttaatacgactcactataggctagcatgagagtgaaggggacacagat 
               
               
                   
               
               
                 gaattggccaaacttgtggaaatgggggactttgatccttgggttggtgatcatgtgtagtgcct 
               
               
                   
               
               
                 cagacaacttgtgggttacagtttattatggagttcctgtgtggagagatgcaaataccacccta 
               
               
                   
               
               
                 ttttgtgcatcagatgccaaagcacatgagacagaagtgcacaatgtctgggccacatatgcctg 
               
               
                   
               
               
                 tgtacccacagatcccaacccacaagaaatacccatggaaaatgtgacagaaaattttaacatgt 
               
               
                   
               
               
                 ggaaaaataacatggtagagcaaatgcaggaggatgtaatcagtttatgggatcaaagtctaaag 
               
               
                   
               
               
                 ccatgtgtaaagttaactcctctctgcgttactttaatttgtaccaatgctaacttgaccaagat 
               
               
                   
               
               
                 caacagtaccaatagcgggcctaaagtaataggaaatgtaacagatgaagtaagaaactgttctt 
               
               
                   
               
               
                 ttaatatgaccacattactaacagataagaagcaaaaggtttatgcacttttttataagcttgat 
               
               
                   
               
               
                 atagtaccaattgataatagtaatagtagtgagtatagattaataaattgtaatacttcagtcat 
               
               
                   
               
               
                 taagcaggcttgtccaaagatatcctttgatccaattcctatacattattgtactccagctggtt 
               
               
                   
               
               
                 atgcgattttaaaatgtaatgataagaatttcaatgggacagggccatgtaaaaatgtcagctca 
               
               
                   
               
               
                 gtacagtgcacacatggaattaagccagtggtctcaactcaattactgttaaatggcagtctagc 
               
               
                   
               
               
                 agaagaagagataataatcagatctgaaaatctcacaaacaatgccaaaaccataatagtgcacc 
               
               
                   
               
               
                 ttaataaggctgtagaaatcaattgtaccagaccctccaacaatacaagaacaagtataagaata 
               
               
                   
               
               
                 ggaccaggacaaatattttatagaacaggagacataataggagatataagacaagcatattgtga 
               
               
                   
               
               
                 aattaatggaacaaaatggaatgaaactttaagacaggtagcaaaaaaattaaaagagcaattta 
               
               
                   
               
               
                 ataacacaataaaattccagccaccctcaggaggagatctagaaattacaatgcttcattttaat 
               
               
                   
               
               
                 tgtagaggggaatttttctattgcaatacaacaaaactgttcaatagtacttgggaaagaaatga 
               
               
                   
               
               
                 gaccataaaagggggtaatggcaatggcaatgacactatcatacttccatgcaggataaagcaaa 
               
               
                   
               
               
                 tcataaacatgtggcaaggagcaggacaagcaatgtatgctcctcccatcagtggaataattaac 
               
               
                   
               
               
                 tgtgtatcaaatattacaggaatactattgacaagagatggtggtaatactaatgaaactgccga 
               
               
                   
               
               
                 gatcttcagacctggaggaggaaatataaaggacaattggagaagtgaattatataaatataaag 
               
               
                   
               
               
                 tagtacaaattgaaccactaggagtagcacccaccaaggcaaagctgacggtacaggccagacaa 
               
               
                   
               
               
                 ttattgtctggtatagtgcaacagcaaagcaatttgctgagggctatagaggcgcagcagcatat 
               
               
                   
               
               
                 gttgcaactcacagtctggggcattaaacagctccaggcaagaatcctggctgtggaaagctacc 
               
               
                   
               
               
                 taaagcatcaacagttcctaggactttggggctgctctaacaaaattatctgcaccactgctgta 
               
               
                   
               
               
                 ccctggaattcctcttggagtaataaatcttatgatgagatttgggaaaatatgacatggataga 
               
               
                   
               
               
                 atgggagagagaaattggcaattacacaaaccaaatatatgatatacttacaaaatcgcaggaac 
               
               
                   
               
               
                 agcaggacaaaaatgaaaaggaactgttggaattggatcaatgggcaagtctgtggaattggttt 
               
               
                   
               
               
                 agcataacaaaatggctgtggtaatgtacaagtaaagcggccgccactgtgctggatgatccgag 
               
               
                   
               
               
                 ctcggtacctctagagtcgacccgggcggccaaaccgctgatcagcctcgactgtgccttctagt 
               
               
                   
               
               
                 tgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccac 
               
               
                   
               
               
                 tgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctgg 
               
               
                   
               
               
                 ggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctggggat 
               
               
                   
               
               
                 gcggtgggctctatggcttctgaggcggaaagaaccagcagatctgcagatctgaattcatctat 
               
               
                   
               
               
                 gtcgggtgcggagaaagaggtaatgaaatggcattatgggtattatgggtctgcattaatgaatc 
               
               
                   
               
               
                 ggccagatatcgatatgctggccaccgtgcatgtgacctcgcacccccgcaagacatggcccgag 
               
               
                   
               
               
                 ttcgagcacaacgtcatgacccgatgcaatgtgcacctggggtcccgccgaggcatgttcatgcc 
               
               
                   
               
               
                 ctaccagtgcaacatgcaatttgtgaaggtgctgctggagcccgatgccatgtccagagtgagcc 
               
               
                   
               
               
                 tgacgggggtgtttgacatgaatgtggagctgtggaaaattctgagatatgatgaatccaagacc 
               
               
                   
               
               
                 aggtgccgggcctgcgaatgcggaggcaagcacgccaggcttcagcccgtgtgtgtggaggtgac 
               
               
                   
               
               
                 ggaggacctgcgacccgatcatttggtgttgtcctgcaacgggacggagttcggctccagcgggg 
               
               
                   
               
               
                 aagaatctgactagagtgagtagtgtttgggggaggtggagggcttgtatgaggggcagaatgac 
               
               
                   
               
               
                 taaaatctgtgtttttctgtgtgttgcagcagcatgagcggaagcgcctcctttgagggaggggt 
               
               
                   
               
               
                 attcagcccttatctgacggggcgtctcccctcctgggcgggagtgcgtcagaatgtgatgggat 
               
               
                   
               
               
                 ccacggtggacggccggcccgtgcagcccgcgaactcttcaaccctgacctacgcgaccctgagc 
               
               
                   
               
               
                 tcctcgtccgtggacgcagctgccgccgcagctgctgcttccgccgccagcgccgtgcgcggaat 
               
               
                   
               
               
                 ggccctgggcgccggctactacagctctctggtggccaactcgacttccaccaataatcccgcca 
               
               
                   
               
               
                 gcctgaacgaggagaagctgctgctgctgatggcccagctcgaggccctgacccagcgcctgggc 
               
               
                   
               
               
                 gagctgacccagcaggtggctcagctgcaggcggagacgcgggccgcggttgccacggtgaaaac 
               
               
                   
               
               
                 caaataaaaaatgaatcaataaataaacggagacggttgttgattttaacacagagtcttgaatc 
               
               
                   
               
               
                 tttatttgatttttcgcgcgcggtaggccctggaccaccggtctcgatcattgagcacccggtgg 
               
               
                   
               
               
                 attttttccaggacccggtagaggtgggcttggatgttgaggtacatgggcatgagcccgtcccg 
               
               
                   
               
               
                 ggggtggaggtagctccattgcagggcctcgtgctcgggggtggtgttgtaaatcacccagtcat 
               
               
                   
               
               
                 agcaggggcgcagggcgtggtgctgcacgatgtccttgaggaggagactgatggccacgggcagc 
               
               
                   
               
               
                 cccttggtgtaggtgttgacgaacctgttgagctgggagggatgcatgcggggggagatgagatg 
               
               
                   
               
               
                 catcttggcctggatcttgagattggcgatgttcccgcccagatcccgccgggggttcatgttgt 
               
               
                   
               
               
                 gcaggaccaccagcacggtgtatccggcgcacttggggaatttgtcatgcaacttggaagggaag 
               
               
                   
               
               
                 gcgtgaaagaatttggagacgcccttgtgaccgcccaggttttccatgcactcatccatgatgat 
               
               
                   
               
               
                 ggcgatgggcccgtgggcggcggcctgggcaaagacgtttcgggggtcggacacatcgtagttgt 
               
               
                   
               
               
                 ggtcctgggtgagctcgtcataggccattttaatgaatttggggcggagggtgcccgactggggg 
               
               
                   
               
               
                 acgaaggtgccctcgatcccgggggcgtagttgccctcgcagatctgcatctcccaggccttgag 
               
               
                   
               
               
                 ctcggagggggggatcatgtccacctgcggggcgatgaaaaaaacggtttccggggcgggggaga 
               
               
                   
               
               
                 tgagctgggccgaaagcaggttccggagcagctgggacttgccgcagccggtggggccgtagatg 
               
               
                   
               
               
                 accccgatgaccggctgcaggtggtagttgagggagagacagctgccgtcctcgcggaggagggg 
               
               
                   
               
               
                 ggccacctcgttcatcatctcgcgcacatgcatgttctcgcgcacgagttccgccaggaggcgct 
               
               
                   
               
               
                 cgccccccagcgagaggagctcttgcagcgaggcgaagtttttcagcggcttgagyccgtcggcc 
               
               
                   
               
               
                 atgggcattttggagagggtctgttgcaagagttccagacggtcccagagctcggtgatgtgctc 
               
               
                   
               
               
                 tagggcatctcgatccagcagacctcctcgtttcgcgggttggggcgactgcgggagtagggcac 
               
               
                   
               
               
                 caggcgatgggcgtccagcgaggccagggtccggtccttccagggtcgcagggtccgcgtcagcg 
               
               
                   
               
               
                 tggtctccgtcacggtgaaggggtgcgcgccgggctgggcgcttgcgagggtgcgcttcaggctc 
               
               
                   
               
               
                 atccggctggtcgagaaccgctcccggtcggcgccctgcgcgtcggccaggtagcaattgagcat 
               
               
                   
               
               
                 gagttcgtagttgagcgcctcggccgcgtggcccttggcgcggagcttacctttggaagtgtgtc 
               
               
                   
               
               
                 cgcagacgggacagaggagggacttgagggcgtagagcttgggggcgaggaagacggactcgggg 
               
               
                   
               
               
                 gcgtaggcgtccgcgccgcagctggcgcagacggtctcgcactccacgagccaggtgaggtcggg 
               
               
                   
               
               
                 ccggttggggtcaaaaacgaggtttcctccgtgctttttgatgcgtttcttacctctggtctcca 
               
               
                   
               
               
                 tgagctcgtgtccccgctgggtgacaaagaggctgtccgtgtccccgtagaccgactttatgggc 
               
               
                   
               
               
                 cggtcctcgagcggggtgccgcggtcctcgtcgtagaggaaccccgcccactccgagacgaaggc 
               
               
                   
               
               
                 ccgggtccaggccagcacgaaggaggccacgtgggaggggtagcggtcgttgtccaccagcgggt 
               
               
                   
               
               
                 ccaccttctccagggtatgcaagcacatgtccccctcgtccacatccaggaaggtgattggcttg 
               
               
                   
               
               
                 taagtgtaggccacgtgaccgggggtcccggccgggggggtataaaagggggcgggcccctgctc 
               
               
                   
               
               
                 gtcctcactgtcttccggatcgctgtccaggagcgccagctgttggggtaggtattccctctcga 
               
               
                   
               
               
                 aggctggcataacctcggcactcaggttgtcagtttctagaaacgaggaggatttgatattgacg 
               
               
                   
               
               
                 gtgccgttggagacgcctttcatgagcccctcgtccatctggtcagaaaagacgatctttttgtt 
               
               
                   
               
               
                 gtcgagcttggtggcgaaggagccgtagagggcgttggagaggagcttggcgatggagcgcatgg 
               
               
                   
               
               
                 tctggttcttttccttgtcggcgcgctccttggcggcgatgttgagctgcacgtactcgcgcgcc 
               
               
                   
               
               
                 acgcacttccattcggggaagacggtggtgagctcgtcgggcacgattctgacccgccagccgcg 
               
               
                   
               
               
                 gttgtgcagggtgatgaggtccacgctggtggccacctcgccgcgcaggggctcgttggtccagc 
               
               
                   
               
               
                 agaggcgcccgcccttgcgcgagcagaaggggggcagcgggtccagcatgagctcgtcggggggg 
               
               
                   
               
               
                 tcggcgtccacggtgaagatgccgggcagaagctcggggtcgaagtagctgatgcaggtgtccag 
               
               
                   
               
               
                 atcgtccagcgccgcttgccagtcgcgcacggccagcgcgcgctcgtaggggctgaggggcgtgc 
               
               
                   
               
               
                 cccagggcatggggtgcgtgagcgcggaggcgtacatgccgcagatgtcgtagacgtagaggggc 
               
               
                   
               
               
                 tcctcgaggacgccgatgtaggtggggtagcagcgccccccgcggatgctggcgcgcacgtagtc 
               
               
                   
               
               
                 gtacagctcgtgcgagggcgcgaggagccccgtgccgaggttggagcgttgcggcttttcggcgc 
               
               
                   
               
               
                 ggtagacgatctggcggaagatggcgtgggagttggaggagatggtgggcctctggaagatgttg 
               
               
                   
               
               
                 aagtgggcgtggggcaggccgaccgagtccctgatgaagtgggcgtaggagtcctgcagcttggc 
               
               
                   
               
               
                 gacgagctcggcggtgacgaggacgtccagggcgcagtagtcgagggtctcttggatgatgtcgt 
               
               
                   
               
               
                 acttgagctggcccttctgcttccacagctcgcggttgagaaggaactcttcgcggtccttccag 
               
               
                   
               
               
                 tactcttcgagggggaacccgtcctgatcggcacggtaagagcccaccatgtagaactggttgac 
               
               
                   
               
               
                 ggccttgtaggcgcagcagcccttctccacggggagggcgtaagcttgtgcggccttgcgcaggg 
               
               
                   
               
               
                 aggtgtgggtgagggcgaaggtgtcgcgcaccatgaccttgaggaactggtgcttgaagtcgagg 
               
               
                   
               
               
                 tcgtcgcagccgccctgctcccagagctggaagtccgtgcgcttcttgtaggcggggttgggcaa 
               
               
                   
               
               
                 agcgaaagtaacatcgttgaagaggatcttgcccgcgcggggcatgaagttgcgagtgatgcgga 
               
               
                   
               
               
                 aaggctggggcacctcggcccggttgttgatgacctgggcggcgaggacgatctcgtcgaagccg 
               
               
                   
               
               
                 ttgatgttgtgcccgacgatgtagagttccacgaatcgcgggcggcccttaacgtggggcagctt 
               
               
                   
               
               
                 cttgagctcgtcgtaggtgagctcggcggggtcgctgagcccgtgctgctcgagggcccagtcgg 
               
               
                   
               
               
                 cgacgtgggggttggcgctgaggaaggaagtccagagatccacggccagggcggtctgcaagcgg 
               
               
                   
               
               
                 tcccggtactgacggaactgctggcccacggccattttttcgggggtgacgcagtagaaggtgcg 
               
               
                   
               
               
                 ggggtcgccgtgccagcggtcccacttgagctggagggcgaggtcgtgggcgagctcgacgagcg 
               
               
                   
               
               
                 gcgggtccccggagagtttcatgaccagcatgaaggggacgagctgcttgccgaaggaccccatc 
               
               
                   
               
               
                 caggtgtaggtttccacatcgtaggtgaggaagagcctttcggtgcgaggatgcgagccgatggg 
               
               
                   
               
               
                 gaagaactggatctcctgccaccagttggaggaatggctgttgatgtgatggaagtagaaatgcc 
               
               
                   
               
               
                 gacggcgcgccgagcactcgtgcttgtgtttatacaagcgtccgcagtgctcgcaacgctgcacg 
               
               
                   
               
               
                 ggatgcacgtgctgcacgagctgtacctgggttcctttgacgaggaatttcagtgggcagtggag 
               
               
                   
               
               
                 cgctggcggctgcatctggtgctgtactacgtcctggccatcggcgtggccatcgtctgcctcga 
               
               
                   
               
               
                 tggtggtcatgctgacgagcccgcgcgggaggcaggtccagacttcggctcggacgggtcggaga 
               
               
                   
               
               
                 gcgaggacgagggcgcgcaggccggagctgtccagggtcctgagacgctgcggagtcaggtcagt 
               
               
                   
               
               
                 gggcagcggcggcgcgcggttgacttgcaggagcttttccagggcgcgcgggaggtccagatggt 
               
               
                   
               
               
                 acttgatctccacggcgccgttggtggcgacgtccacggcttgcagggtcccgtgcccctggggc 
               
               
                   
               
               
                 gccaccaccgtgccccgtttcttcttgggcgctgcttccatgccggtcagaagcggcggcgagga 
               
               
                   
               
               
                 cgcgcgccgggcggcaggggcggctcgggacccggaggcaggggcggcaggggcacgtcggcgcc 
               
               
                   
               
               
                 gcgcgcgggcaggttctggtactgcgcccggagaagactggcgtgagcgacgacgcgacggttga 
               
               
                   
               
               
                 cgtcctggatctgacgcctctgggtgaaggccacgggacccgtgagtttgaacctgaaagagagt 
               
               
                   
               
               
                 tcgacagaatcaatctcggtatcgttgacggcggcctgccgcaggatctcttgcacgtcgcccga 
               
               
                   
               
               
                 gttgtcctggtaggcgatctcggtcatgaactgctcgatctcctcctcctgaaggtctccgcggc 
               
               
                   
               
               
                 cggcgcgctcgacggtggccgcgaggtcgttggagatgcggcccatgagctgcgagaaggcgttc 
               
               
                   
               
               
                 atgccggcctcgttccagacgcggctgtagaccacggctccgtcggggtcgcgcgcgcgcatgac 
               
               
                   
               
               
                 cacctgggcgaggttgagctcgacgtggcgcgtgaagaccgcgtagttgcagaggcgctggtaga 
               
               
                   
               
               
                 ggtagttgagcgtggtggcgatgtgctcggtgacgaagaagtacatgatccagcggcggagcggc 
               
               
                   
               
               
                 atctcgctgacgtcgcccagggcttccaagcgctccatggcctcgtagaagtccacggcgaagtt 
               
               
                   
               
               
                 gaaaaactgggagttgcgcgccgagacggtcaactcctcctccagaagacggatgagctcagcga 
               
               
                   
               
               
                 tggtggcgcgcacctcgcgctcgaaggccccggggggctcctcttcttccatctcttcctcctcc 
               
               
                   
               
               
                 actaacatctcttctacttcctcctcaggaggcggcggcgggggaggggccctgcgtcgccggcg 
               
               
                   
               
               
                 gcgcacgggcagacggtcgatgaagcgctcgatggtctccccgcgccggcgacgcatggtctcgg 
               
               
                   
               
               
                 tgacggcgcgcccgtcctcgcggggccgcagcgtgaagacgccgccgcgcatctccaggtggccg 
               
               
                   
               
               
                 ccgggggggtctccgttgggcagggagagggcgctgacgatgcatcttatcaattggcccgtagg 
               
               
                   
               
               
                 gactccgcgcaaggacctgagcgtctcgagatccacgggatccgaaaaccgctgaacgaaggctt 
               
               
                   
               
               
                 cgagccagtcgcagtcgcaaggtaggctgagcccggtttcttgttcttcggggatttcgggaggc 
               
               
                   
               
               
                 gggcgggcgatgctgctggtgatgaagttgaagtaggcggtcctgagacggcggatggtggcgag 
               
               
                   
               
               
                 gagcaccaggtccttgggcccggcttgctggatgcgcagacggtcggccatgccccaggcgtggt 
               
               
                   
               
               
                 cctgacacctggcgaggtccttgtagtagtcctgcatgagccgctccacgggcacctcctcctcg 
               
               
                   
               
               
                 cccgcgcggccgtgcatgcgcgtgagcccgaacccgcgctggggctggacgagcgccaggtcggc 
               
               
                   
               
               
                 gacgacgcgctcggcgaggatggcctgctgtatctgggtgagggtggtctggaagtcgtcgaagt 
               
               
                   
               
               
                 cgacgaagcggtggtaggctccggtgttgatggtataggagcagttggccatgacggaccagttg 
               
               
                   
               
               
                 acggtctggtggccgggtcgcacgagctcgtggtacttgaggcgcgagtaggcgcgcgtgtcgaa 
               
               
                   
               
               
                 gatgtagtcgttgcaggtgcgcacgaggtactggtatccgacgaggaagtgcggcggcggctggc 
               
               
                   
               
               
                 ggtagagcggccatcgctcggtggcgggggcgccgggcgcgaggtcctcgagcatgaggcggtgg 
               
               
                   
               
               
                 tagccgtagatgtacctggacatccaggtgatgccggcggcggtggtggaggcgcgcgggaactc 
               
               
                   
               
               
                 gcggacgcggttccagatgttgcgcagcggcaggaagtagttcatggtggccgcggtctggcccg 
               
               
                   
               
               
                 tgaggcgcgcgcagtcgtggatgctctagacatacgggcaaaaacgaaagcggtcagcggctcga 
               
               
                   
               
               
                 ctccgtggcctggaggctaagcgaacgggttgggctgcgcgtgtaccccggttcgaatctcgaat 
               
               
                   
               
               
                 caggctggagccgcagctaacgtggtactggcactcccgtctcgacccaagcctgctaacgaaac 
               
               
                   
               
               
                 ctccaggatacggaggcgggtcgttttttggccttggtcgctggtcatgaaaaactagtaagcgc 
               
               
                   
               
               
                 ggaaagcgaccgcccgcgatggctcgctgccgtagtctggagaaagaatcgccagggttgcgttg 
               
               
                   
               
               
                 cggtgtgccccggttcgagcctcagcgctcggcgccggccggattccgcggctaacgtgggcgtg 
               
               
                   
               
               
                 gctgccccgtcgtttccaagaccccttagccagccgacttctccagttacggagcgagcccctct 
               
               
                   
               
               
                 ttttcttgtgtttttgccagatgcatcccgtactgcggcagatgcgcccccaccctccacctcaa 
               
               
                   
               
               
                 ccgcccctaccgccgcagcagcagcaacagccggcgcttctgcccccgccccagcagcagccagc 
               
               
                   
               
               
                 cactaccgcggcggccgccgtgagcggagccggcgttcagtatgacctggccttggaagagggcg 
               
               
                   
               
               
                 aggggctggcgcggctgggggcgtcgtcgccggagcggcacccgcgcgtgcagatgaaaagggac 
               
               
                   
               
               
                 gctcgcgaggcctacgtgcccaagcagaacctgttcagagacaggagcggcgaggagcccgagga 
               
               
                   
               
               
                 gatgcgcgcctcccgcttccacgcggggcgggagctgcggcgcggcctggaccgaaagcgggtgc 
               
               
                   
               
               
                 tgagggacgaggatttcgaggcggacgagctgacggggatcagccccgcgcgcgcgcacgtggcc 
               
               
                   
               
               
                 gcggccaacctggtcacggcgtacgagcagaccgtgaaggaggagagcaacttccaaaaatcctt 
               
               
                   
               
               
                 caacaaccacgtgcgcacgctgatcgcgcgcgaggaggtgaccctgggcctgatgcacctgtggg 
               
               
                   
               
               
                 acctgctggaggccatcgtgcagaaccccacgagcaagccgctgacggcgcagctgtttctggtg 
               
               
                   
               
               
                 gtgcagcacagtcgggacaacgagacgttcagggaggcgctgctgaatatcaccgagcccgaggg 
               
               
                   
               
               
                 ccgctggctcctggacctggtgaacattctgcagagcatcgtggtgcaggagcgcgggctgccgc 
               
               
                   
               
               
                 tgtccgagaagctggcggctatcaacttctcggtgctgagcctgggcaagtactacgctaggaag 
               
               
                   
               
               
                 atctacaagaccccgtacgtgcccatagacaaggaggtgaagatcgacgggttttacatgcgcat 
               
               
                   
               
               
                 gaccctgaaagtgctgaccctgagcgacgatctgggggtgtaccgcaacgacaggatgcaccgcg 
               
               
                   
               
               
                 cggtgagcgccagccgccggcgcgagctgagcgaccaggagctgatgcacagcctgcagcgggcc 
               
               
                   
               
               
                 ctgaccggggccgggaccgagggggagagctactttgacatgggcgcggacctgcgctggcagcc 
               
               
                   
               
               
                 cagccgccgggccttggaagctgccggcggttccccctacgtggaggaggtggacgatgaggagg 
               
               
                   
               
               
                 aggagggcgagtacctggaagactgatggcgcgaccgtatttttgctagatgcagcaacagccac 
               
               
                   
               
               
                 cgcctcctgatcccgcgatgcgggcggcgctgcagagccagccgtccggcattaactcctcggac 
               
               
                   
               
               
                 gattggacccaggccatgcaacgcatcatggcgctgacgacccgcaatcccgaagcctttagaca 
               
               
                   
               
               
                 gcagcctcaggccaaccggctctcggccatcctggaggccgtggtgccctcgcgctcgaacccca 
               
               
                   
               
               
                 cgcacgagaaggtgctggccatcgtgaacgcgctggtggagaacaaggccatccgcggcgacgag 
               
               
                   
               
               
                 gccgggctggtgtacaacgcgctgctggagcgcgtggcccgctacaacagcaccaacgtgcagac 
               
               
                   
               
               
                 gaacctggaccgcatggtgaccgacgtgcgcgaggcggtgtcgcagcgcgagcggttccaccgcg 
               
               
                   
               
               
                 agtcgaacctgggctccatggtggcgctgaacgccttcctgagcacgcagcccgccaacgtgccc 
               
               
                   
               
               
                 cggggccaggaggactacaccaacttcatcagcgcgctgcggctgatggtggccgaggtgcccca 
               
               
                   
               
               
                 gagcgaggtgtaccagtcggggccggactacttcttccagaccagtcgccagggcttgcagaccg 
               
               
                   
               
               
                 tgaacctgagccaggctttcaagaacttgcagggactgtggggcgtgcaggccccggtcggggac 
               
               
                   
               
               
                 cgcgcgacggtgtcgagcctgctgacgccgaactcgcgcctgctgctgctgctggtggcgccctt 
               
               
                   
               
               
                 cacggacagcggcagcgtgagccgcgactcgtacctgggctacctgcttaacctgtaccgcgagg 
               
               
                   
               
               
                 ccatcgggcaggcgcacgtggacgagcagacctaccaggagatcacccacgtgagccgcgcgctg 
               
               
                   
               
               
                 ggccaggaggacccgggcaacctggaggccaccctgaacttcctgctgaccaaccggtcgcagaa 
               
               
                   
               
               
                 gatcccgccccagtacgcgctgagcaccgaggaggagcgcatcctgcgctacgtgcagcagagcg 
               
               
                   
               
               
                 tggggctgttcctgatgcaggagggggccacgcccagcgccgcgctcgacatgaccgcgcgcaac 
               
               
                   
               
               
                 atggagcccagcatgtacgctcgcaaccgcccgttcatcaataagctgatggactacttgcatcg 
               
               
                   
               
               
                 ggcggccgccatgaactcggactactttaccaacgccatcttgaacccgcactggctcccgccgc 
               
               
                   
               
               
                 ccgggttctacacgggcgagtacgacatgcccgaccccaacgacgggttcctgtgggacgacgtg 
               
               
                   
               
               
                 gacagcagcgtgttctcgccgcgccccgccaccaccgtgtggaagaaagagggcggggaccggcg 
               
               
                   
               
               
                 gccgtcctcggcgctgtccggtcgcgcgggtgctgccgcggcggtgcctgaggccgccagcccct 
               
               
                   
               
               
                 tcccgagcctgcccttttcgctgaacagcgtgcgcagcagcgagctgggtcggctgacgcggccg 
               
               
                   
               
               
                 cgcctgctgggcgaggaggagtacctgaacgactccttgttgaggcccgagcgcgagaagaactt 
               
               
                   
               
               
                 ccccaataacgggatagagagcctggtggacaagatgagccgctggaagacgtacgcgcacgagc 
               
               
                   
               
               
                 acagggacgagccccgagctagcagcagcgcaggcacccgtagacgccagcgacacgacaggcag 
               
               
                   
               
               
                 cggggtctggtgtgggacgatgaggattccgccgacgacagcagcgtgttggacttgggtgggag 
               
               
                   
               
               
                 tggtggtggtaacccgttcgctcacttgcgcccccgtatcgggcgcctgatgtaagaatctgaaa 
               
               
                   
               
               
                 aaataaaaaacggtactcaccaaggccatggcgaccagcgtgcgttcttctctgttgtttgtagt 
               
               
                   
               
               
                 agtatgatgaggcgcgtgtacccggagggtcctcctccctcgtacgagagcgtgatgcagcaggc 
               
               
                   
               
               
                 ggtggcggcggcgatgcagcccccgctggaggcgccttacgtgcccccgcggtacctggcgccta 
               
               
                   
               
               
                 cggaggggcggaacagcattcgttactcggagctggcacccttgtacgataccacccggttgtac 
               
               
                   
               
               
                 ctggtggacaacaagtcggcggacatcgcctcgctgaactaccagaacgaccacagcaacttcct 
               
               
                   
               
               
                 gaccaccgtggtgcagaacaacgatttcacccccacggaggccagcacccagaccatcaactttg 
               
               
                   
               
               
                 acgagcgctcgcggtggggcggccagctgaaaaccatcatgcacaccaacatgcccaacgtgaac 
               
               
                   
               
               
                 gagttcatgtacagcaacaagttcaaggcgcgggtgatggtctcgcgcaagacccccaatggggt 
               
               
                   
               
               
                 cgcggtggatgagaattatgatggtagtcaggacgagctgacttacgagtgggtggagtttgagc 
               
               
                   
               
               
                 tgcccgagggcaacttctcggtgaccatgaccatcgatctgatgaacaacgccatcatcgacaac 
               
               
                   
               
               
                 tacttggcggtggggcgtcagaacggggtgctggagagcgacatcggcgtgaagttcgacacgcg 
               
               
                   
               
               
                 caacttccggctgggctgggaccccgtgaccgagctggtgatgccgggcgtgtacaccaacgagg 
               
               
                   
               
               
                 ccttccaccccgacatcgtcctgctgcccggctgcggcgtggacttcaccgagagccgcctcagc 
               
               
                   
               
               
                 aacctgctgggcatccgcaagcggcagcccttccaggagggcttccagatcctgtacgaggacct 
               
               
                   
               
               
                 ggaggggggcaacatccccgcgctcttggatgtcgaagcctatgagaaaagcaaggaggaggccg 
               
               
                   
               
               
                 ccgcagcggcgaccgcagccgtggccaccgcctctaccgaggtgcggggcgataattttgctagc 
               
               
                   
               
               
                 gccgcggcagtggccgaggcggctgaaaccgaaagtaagatagtcatccagccggtggagaagga 
               
               
                   
               
               
                 cagcaaggacaggagctacaacgtgctcgcggacaagaaaaacaccgcctaccgcagctggtacc 
               
               
                   
               
               
                 tggcctacaactacggcgaccccgagaagggcgtgcgctcctggacgctgctcaccacctcggac 
               
               
                   
               
               
                 gtcacctgcggcgtggagcaagtctactggtcgctgcccgacatgatgcaagacccggtcacctt 
               
               
                   
               
               
                 ccgctccacgcgtcaagttagcaactacccggtggtgggcgccgagctcctgcccgtctactcca 
               
               
                   
               
               
                 agagcttcttcaacgagcaggccgtctactcgcagcagctgcgcgccttcacctcgctcacgcac 
               
               
                   
               
               
                 gtcttcaaccgcttccccgagaaccagatcctcgtccgcccgcccgcgcccaccattaccaccgt 
               
               
                   
               
               
                 cagtgaaaacgttcctgctctcacagatcacgggaccctgccgctgcgcagcagtatccggggag 
               
               
                   
               
               
                 tccagcgcgtgaccgtcactgacgccagacgccgcacctgcccctacgtctacaaggccctgggc 
               
               
                   
               
               
                 gtagtcccagcaagatgtacggaggcgctcgccaacgctccacgcaacaccccgtgcgcgtgcgc 
               
               
                   
               
               
                 gggcacttccgcgctccctggggcgccctcaagggccgcgtgcgctcgcgcaccaccgtcgacga 
               
               
                   
               
               
                 cgtgatcgaccaggtggtggccgacgcgcgcaactacacgcccgccgccgcgcccgcctccaccg 
               
               
                   
               
               
                 tggacgccgtcatcgacagcgtggtggccgatgcgcgccggtacgcccgcgccaagagccggcgg 
               
               
                   
               
               
                 cggcgcatcgcccggcggcaccggagcacccccgccatgcgcgcggcgcgagccttgctgcgcag 
               
               
                   
               
               
                 ggccaggcgcacgggacgcagggccatgctcagggcggccagacgcgcggcctccggcagcagca 
               
               
                   
               
               
                 gcgccggcaggacccgcagacgcgcggccacggcggcggcggcggccatcgccagcatgtcccgc 
               
               
                   
               
               
                 ccgcggcgcggcaacgtgtactgggtgcgcgacgccgccaccggtgtgcgcgtgcccgtgcgcac 
               
               
                   
               
               
                 ccgcccccctcgcacttgaagatgctgacttcgcgatgttgatgtgtcccagcggcgaggaggat 
               
               
                   
               
               
                 gtccaagcgcaaatacaaggaagagatgctccaggtcatcgcgcctgagatctacggccccgcgg 
               
               
                   
               
               
                 tgaaggaggaaagaaagccccgcaaactgaagcgggtcaaaaaggacaaaaaggaggaggaagat 
               
               
                   
               
               
                 gtggacggactggtggagtttgtgcgcgagttcgccccccggcggcgcgtgcagtggcgcgggcg 
               
               
                   
               
               
                 gaaagtgaaaccggtgctgcggcccggcaccacggtggtcttcacgcccggcgagcgttccggct 
               
               
                   
               
               
                 ccgcctccaagcgctcctacgacgaggtgtacggggacgaggacatcctcgagcaggcggtcgag 
               
               
                   
               
               
                 cgtctgggcgagtttgcttacggcaagcgcagccgccccgcgcccttgaaagaggaggcggtgtc 
               
               
                   
               
               
                 catcccgctggaccacggcaaccccacgccgagcctgaagccggtgaccctgcagcaggtgctgc 
               
               
                   
               
               
                 cgagcgcggcgccgcgccggggcttcaagcgcgagggcggcgaggatctgtacccgaccatgcag 
               
               
                   
               
               
                 ctgatggtgcccaagcgccagaagctggaggacgtgctggagcacatgaaggtggaccccgaggt 
               
               
                   
               
               
                 gcagcccgaggtcaaggtgcggcccatcaagcaggtggccccgggcctgggcgtgcagaccgtgg 
               
               
                   
               
               
                 acatcaagatccccacggagcccatggaaacgcagaccgagcccgtgaagcccagcaccagcacc 
               
               
                   
               
               
                 atggaggtgcagacggatccctggatgccggcgccggcttccaccactcgccgaagacgcaagta 
               
               
                   
               
               
                 cggcgcggccagcctgctgatgcccaactacgcgctgcatccttccatcatccccacgccgggct 
               
               
                   
               
               
                 accgcggcacgcgcttctaccgcggctacaccagcagccgccgcaagaccaccacccgccgccgc 
               
               
                   
               
               
                 cgtcgtcgcacccgccgcagcagcaccgcgacttccgccgccgccctggtgcggagagtgtaccg 
               
               
                   
               
               
                 cagcgggcgcgagcctctgaccctgccgcgcgcgcgctaccacccgagcatcgccatttaactct 
               
               
                   
               
               
                 gccgtcgcctcctacttgcagatatggccctcacatgccgcctccgcgtccccattacgggctac 
               
               
                   
               
               
                 cgaggaagaaagccgcgccgtagaaggctgacggggaacgggctgcgtcgccatcaccaccggcg 
               
               
                   
               
               
                 gcggcgcgccatcagcaagcggttggggggaggcttcctgcccgcgctgatccccatcatcgccg 
               
               
                   
               
               
                 cggcgatcggggcgatccccggcatagcttccgtggcggtgcaggcctctcagcgccactgagac 
               
               
                   
               
               
                 acagcttggaaaatttgtaataaaaaaatggactgacgctcctggtcctgtgatgtgtgttttta 
               
               
                   
               
               
                 gatggaagacatcaatttttcgtccctggcaccgcgacacggcacgcggccgtttatgggcacct 
               
               
                   
               
               
                 ggagcgacatcggcaacagccaactgaacgggggcgccttcaattggagcagtctctggagcggg 
               
               
                   
               
               
                 cttaagaatttcgggtccacgctcaaaacctatggcaacaaggcgtggaacagcagcacagggca 
               
               
                   
               
               
                 ggcgctgagggaaaagctgaaagagcagaacttccagcagaaggtggtcgatggcctggcctcgg 
               
               
                   
               
               
                 gcatcaacggggtggtggacctggccaaccaggccgtgcagaaacagatcaacagccgcctggac 
               
               
                   
               
               
                 gcggtcccgcccgcggggtccgtggagatgccccaggtggaggaggagctgcctcccctggacaa 
               
               
                   
               
               
                 gcgcggcgacaagcgaccgcgtcccgacgcggaggagacgctgctgacgcacacggacgagccgc 
               
               
                   
               
               
                 ccccgtacgaggaggcggtgaaactgggtctgcccaccacgcggcccgtggcgcctctggccacc 
               
               
                   
               
               
                 ggggtgctgaaacccagcagcagcagccagcccgcgaccctggacttgcctccgcctgcttcccg 
               
               
                   
               
               
                 cccctccacagtggctaagcccctgccgccggtggccgtcgcgtcgcgcgccccccgaggccgcc 
               
               
                   
               
               
                 cccaggcgaactggcagagcactctgaacagcatcgtgggtctgggagtgcagagtgtgaagcgc 
               
               
                   
               
               
                 cgccgctgctattaaaagacactgtagcgcttaacttgcttgtctgtgtgtatatgtatgtccgc 
               
               
                   
               
               
                 cgaccagaaggaggaagaggcgcgtcgccgagttgcaagatggccaccccatcgatgctgcccca 
               
               
                   
               
               
                 gtgggcgtacatgcacatcgccggacaggacgcttcggagtacctgagtccgggtctggtgcagt 
               
               
                   
               
               
                 tcgcccgcgccacagacacctacttcagtctggggaacaagtttaggaaccccacggtggcgccc 
               
               
                   
               
               
                 acgcacgatgtgaccaccgaccgcagccagcggctgacgctgcgcttcgtgcccgtggaccgcga 
               
               
                   
               
               
                 ggacaacacctactcgtacaaagtgcgctacacgctggccgtgggcgacaaccgcgtgctggaca 
               
               
                   
               
               
                 tggccagcacctactttgacatccgcggcgtgctggatcgggggcccagcttcaaaccctactcc 
               
               
                   
               
               
                 ggcaccgcctacaacagcctggctcccaagggagcgcccaacacttgccagtggacatataaagc 
               
               
                   
               
               
                 tggtgatactgatacagaaaaaacctatacatatggaaatgcacctgtgcaaggcattagcatta 
               
               
                   
               
               
                 caaaggatggtattcaacttggaactgacagcgatggtcaggcaatctatgcagacgaaacttat 
               
               
                   
               
               
                 caaccagagcctcaagtgggtgatgctgaatggcatgacatcactggtactgatgaaaaatatgg 
               
               
                   
               
               
                 aggcagagctcttaagcctgacaccaaaatgaagccttgctatggttcttttgccaagcctacca 
               
               
                   
               
               
                 ataaagaaggaggccaggcaaatgtgaaaaccgaaacaggcggtaccaaagaatatgacattgac 
               
               
                   
               
               
                 atggcattcttcgataatcgaagtgcagctgccgccggcctagccccagaaattgttttgtatac 
               
               
                   
               
               
                 tgagaatgtggatctggaaactccagatacccatattgtatacaaggcaggtacagatgacagta 
               
               
                   
               
               
                 gctcttctatcaatttgggtcagcagtccatgcccaacagacccaactacattggcttcagagac 
               
               
                   
               
               
                 aactttatcggtctgatgtactacaacagcactggcaatatgggtgtactggctggacaggcctc 
               
               
                   
               
               
                 ccagctgaatgctgtggtggacttgcaggacagaaacaccgaactgtcctaccagctcttgcttg 
               
               
                   
               
               
                 actctctgggtgacagaaccaggtatttcagtatgtggaatcaggcggtggacagttatgacccc 
               
               
                   
               
               
                 gatgtgcgcattattgaaaatcacggtgtggaggatgaacttcctaactattgcttccccctgga 
               
               
                   
               
               
                 tgctgtgggtagaactgatacttaccagggaattaaggccaatggtgataatcaaaccacctgga 
               
               
                   
               
               
                 ccaaagatgatactgttaatgatgctaatgaattgggcaagggcaatcctttcgccatggagatc 
               
               
                   
               
               
                 aacatccaggccaacctgtggcggaacttcctctacgcgaacgtggcgctgtacctgcccgactc 
               
               
                   
               
               
                 ctacaagtacacgccggccaacatcacgctgcccaccaacaccaacacctacgattacatgaacg 
               
               
                   
               
               
                 gccgcgtggtggcgccctcgctggtggacgcctacatcaacatcggggcgcgctggtcgctggac 
               
               
                   
               
               
                 cccatggacaacgtcaaccccttcaaccaccaccgcaacgcgggcctgcgataccgctccatgct 
               
               
                   
               
               
                 cctgggcaacgggcgctacgtgcccttccacatccaggtgccccaaaagtttttcgccatcaaga 
               
               
                   
               
               
                 gcctcctgctcctgcccgggtcctacacctacgagtggaacttccgcaaggacgtcaacatgatc 
               
               
                   
               
               
                 ctgcagagctccctcggcaacgacctgcgcacggacggggcctccatcgccttcaccagcatcaa 
               
               
                   
               
               
                 cctctacgccaccttcttccccatggcgcacaacaccgcctccacgctcgaggccatgctgcgca 
               
               
                   
               
               
                 acgacaccaacgaccagtccttcaacgactacctctcggcggccaacatgctctaccccatcccg 
               
               
                   
               
               
                 gccaacgccaccaacgtgcccatctccatcccctcgcgcaactgggccgccttccgcggctggtc 
               
               
                   
               
               
                 cttcacgcgcctcaagacccgcgagacgccctcgctcggctccgggttcgacccctacttcgtct 
               
               
                   
               
               
                 actcgggctccatcccctacctcgacggcaccttctacctcaaccacaccttcaagaaggtctcc 
               
               
                   
               
               
                 atcaccttcgactcctccgtcagctggcccggcaacgaccgcctcctgacgcccaacgagttcga 
               
               
                   
               
               
                 aatcaagcgcaccgtcgacggagaggggtacaacgtggcccagtgcaacatgaccaaggactggt 
               
               
                   
               
               
                 tcctggtccagatgctggcccactacaacatcggctaccagggcttctacgtgcccgagggctac 
               
               
                   
               
               
                 aaggaccgcatgtactccttcttccgcaacttccagcccatgagccgccaggtcgtggacgaggt 
               
               
                   
               
               
                 caactacaaggactaccaggccgtcaccctggcctaccagcacaacaactcgggcttcgtcggct 
               
               
                   
               
               
                 acctcgcgcccaccatgcgccagggccagccctaccccgccaactacccctacccgctcatcggc 
               
               
                   
               
               
                 aagagcgccgtcgccagcgtcacccagaaaaagttcctctgcgaccgggtcatgtggcgcatccc 
               
               
                   
               
               
                 cttctccagcaacttcatgtccatgggcgcgctcaccgacctcggccagaacatgctctacgcca 
               
               
                   
               
               
                 actccgcccacgcgctagacatgaatttcgaagtcgaccccatggatgagtccacccttctctat 
               
               
                   
               
               
                 gttgtcttcgaagtcttcgacgtcgtccgagtgcaccagccccaccgcggcgtcatcgaggccgt 
               
               
                   
               
               
                 ctacctgcgcacgcccttctcggccggcaacgccaccacctaagcctcttgcttcttgcaagatg 
               
               
                   
               
               
                 acggcctgcgcgggctccggcgagcaggagctcagggccatcctccgcgacctgggctgcgggcc 
               
               
                   
               
               
                 ctgcttcctgggcaccttcgacaagcgcttcccgggattcatggccccgcacaagctggcctgcg 
               
               
                   
               
               
                 ccatcgtcaacacggccggccgcgagaccgggggcgagcactggctggccttcgcctggaacccg 
               
               
                   
               
               
                 cgctcccacacctgctacctcttcgaccccttcgggttctcggacgagcgcctcaagcagatcta 
               
               
                   
               
               
                 ccagttcgagtacgagggcctgctgcgtcgcagcgccctggccaccgaggaccgctgcgtcaccc 
               
               
                   
               
               
                 tggaaaagtccacccagaccgtgcagggtccgcgctcggccgcctgcgggctcttctgctgcatg 
               
               
                   
               
               
                 ttcctgcacgccttcgtgcactggcccgaccgccccatggacaagaaccccaccatgaacttgct 
               
               
                   
               
               
                 gacgggggtgcccaacggcatgctccagtcgccccaggtggaacccaccctgcgccgcaaccagg 
               
               
                   
               
               
                 aggcgctctaccgcttcctcaacgcccactccgcctactttcgctcccaccgcgcgcgcatcgag 
               
               
                   
               
               
                 aaggccaccgccttcgaccgcatgaatcaagacatgtaatccggtgtgtgtatgtgaatgcttta 
               
               
                   
               
               
                 ttcatcataataaacagcacatgtttatgccaccttctctgaggctctgactttatttagaaatc 
               
               
                   
               
               
                 gaaggggttctgccggctctcggcatggcccgcgggcagggatacgttgcggaactggtacttgg 
               
               
                   
               
               
                 gcagccacttgaactcggggatcagcagcttcggcacggggaggtcggggaacgagtcgctccac 
               
               
                   
               
               
                 agcttgcgcgtgagttgcagggcgcccagcaggtcgggcgcggagatcttgaaatcgcagttggg 
               
               
                   
               
               
                 acccgcgttctgcgcgcgagagttacggtacacggggttgcagcactggaacaccatcagggccg 
               
               
                   
               
               
                 ggtgcttcacgctcgccagcaccgtcgcgtcggtgatgccctccacgtccagatcctcggcgttg 
               
               
                   
               
               
                 gccatcccgaagggggtcatcttgcaggtctgccgccccatgctgggcacgcagccgggcttgtg 
               
               
                   
               
               
                 gttgcaatcgcagtgcagggggatcagcatcatctgggcctgctcggagctcatgcccgggtaca 
               
               
                   
               
               
                 tggccttcatgaaagcctccagctggcggaaggcctgctgcgccttgccgccctcggtgaagaag 
               
               
                   
               
               
                 accccgcaggacttgctagagaactggttggtggcgcagccagcgtcgtgcacgcagcagcgcgc 
               
               
                   
               
               
                 gtcgttgttggccagctgcaccacgctgcgcccccagcggttctgggtgatcttggcccggtcgg 
               
               
                   
               
               
                 ggttctccttcagcgcgcgctgcccgttctcgctcgccacatccatctcgatcgtgtgctccttc 
               
               
                   
               
               
                 tggatcatcacggtcccgtgcaggcaccgcagcttgccctcggcctcggtgcacccgtgcagcca 
               
               
                   
               
               
                 cagcgcgcagccggtgctctcccagttcttgtgggcgatctgggagtgcgagtgcacgaagccct 
               
               
                   
               
               
                 gcaggaagcggcccatcatcgtggtcagggtcttgttgctggtgaaggtcagcggaatgccgcgg 
               
               
                   
               
               
                 tgctcctcgttcacatacaggtggcagatacggcggtacacctcgccctgctcgggcatcagctg 
               
               
                   
               
               
                 gaaggcggacttcaggtcgctctccacgcggtaccggtccatcagcagcgtcatcacttccatgc 
               
               
                   
               
               
                 ccttctcccaggccgaaacgatcggcaggctcagggggttcttcaccgttgtcatcttagtcgcc 
               
               
                   
               
               
                 gccgccgaagtcagggggtcgttctcgtccagggtctcaaacactcgcttgccgtccttctcggt 
               
               
                   
               
               
                 gatgcgcacggggggaaagctgaagcccacggccgccagctcctcctcggcctgcctttcgtcct 
               
               
                   
               
               
                 cgctgtcctggctgatgtcttgcaaaggcacatgcttggtcttgcggggtttctttttgggcggc 
               
               
                   
               
               
                 agaggcggcggcggagacgtgctgggcgagcgcgagttctcgctcaccacgactatttcttctcc 
               
               
                   
               
               
                 ttggccgtcgtccgagaccacgcggcggtaggcatgcctcttctggggcagaggcggaggcgacg 
               
               
                   
               
               
                 ggctctcgcggttcggcgggcggctggcagagccccttccgcgttcgggggtgcgctcctggcgg 
               
               
                   
               
               
                 cgctgctctgactgacttcctccgcggccggccattgtgttctcctagggagcaagcatggagac 
               
               
                   
               
               
                 tcagccatcgtcgccaacatcgccatctgcccccgccgccgccgacgagaaccagcagcagcaga 
               
               
                   
               
               
                 atgaaagcttaaccgccccgccgcccagccccacctccgacgccgcagccccagacatgcaagag 
               
               
                   
               
               
                 atggaggaatccatcgagattgacctgggctacgtgacgcccgcggagcacgaggaggagctggc 
               
               
                   
               
               
                 agcgcgcttttcagccccggaagagaaccaccaagagcagccagagcaggaagcagagagcgagc 
               
               
                   
               
               
                 agaaccaggctgggctcgagcatggcgactacctgagcggggcagaggacgtgctcatcaagcat 
               
               
                   
               
               
                 ctggcccgccaatgcatcatcgtcaaggacgcgctgctcgaccgcgccgaggtgcccctcagcgt 
               
               
                   
               
               
                 ggcggagctcagccgcgcctacgagcgcaacctcttctcgccgcgcgtgccccccaagcgccagc 
               
               
                   
               
               
                 ccaacggcacctgcgagcccaacccgcgcctcaacttctacccggtcttcgcggtgcccgaggcc 
               
               
                   
               
               
                 ctggccacctaccacctctttttcaagaaccaaaggatccccgtctcctgccgcgccaaccgcac 
               
               
                   
               
               
                 ccgcgccgacgccctgctcaacctgggccccggcgcccgcctacctgatatcgcctccttggaag 
               
               
                   
               
               
                 aggttcccaagatcttcgagggtctgggcagcgacgagactcgggccgcgaacgctctgcaagga 
               
               
                   
               
               
                 agcggagaggagcatgagcaccacagcgccctggtggagttggaaggcgacaacgcgcgcctggc 
               
               
                   
               
               
                 ggtcctcaagcgcacggtcgagctgacccacttcgcctacccggcgctcaacctgccccccaagg 
               
               
                   
               
               
                 tcatgagcgccgtcatggaccaggtgctcatcaagcgcgcctcgcccctctcggaggaggagatg 
               
               
                   
               
               
                 caggaccccgagagctcggacgagggcaagcccgtggtcagcgacgagcagctggcgcgctggct 
               
               
                   
               
               
                 gggagcgagtagcaccccccagagcctggaagagcggcgcaagctcatgatggccgtggtcctgg 
               
               
                   
               
               
                 tgaccgtggagctggagtgtctgcgccgcttcttcgccgacgcggagaccctgcgcaaggtcgag 
               
               
                   
               
               
                 gagaacctgcactacctcttcagacacgggttcgtgcgccaggcctgcaagatctccaacgtgga 
               
               
                   
               
               
                 gctgaccaacctggtctcctacatgggcatcctgcacgagaaccgcctggggcagaacgtgctgc 
               
               
                   
               
               
                 acaccaccctgcgcggggaggcccgccgcgactacatccgcgactgcgtctacctgtacctctgc 
               
               
                   
               
               
                 cacacctggcagacgggcatgggcgtgtggcagcagtgcctggaggagcagaacctgaaagagct 
               
               
                   
               
               
                 ctgcaagctcctgcagaagaacctcaaggccctgtggaccgggttcgacgagcgcaccaccgccg 
               
               
                   
               
               
                 cggacctggccgacctcatcttccccgagcgcctgcggctgacgctgcgcaacgggctgcccgac 
               
               
                   
               
               
                 tttatgagccaaagcatgttgcaaaactttcgctctttcatcctcgaacgctccgggatcctgcc 
               
               
                   
               
               
                 cgccacctgctccgcgctgccctcggacttcgtgccgctgaccttccgcgagtgccccccgccgc 
               
               
                   
               
               
                 tctggagccactgctacctgctgcgcctggccaactacctggcctaccactcggacgtgatcgag 
               
               
                   
               
               
                 gacgtcagcggcgagggcctgctcgagtgccactgccgctgcaacctctgcacgccgcaccgctc 
               
               
                   
               
               
                 cctggcctgcaacccccagctgctgagcgagacccagatcatcggcaccttcgagttgcaaggcc 
               
               
                   
               
               
                 ccggcgagggcaaggggggtctgaaactcaccccggggctgtggacctcggcctacttgcgcaag 
               
               
                   
               
               
                 ttcgtgcccgaggactaccatcccttcgagatcaggttctacgaggaccaatcccagccgcccaa 
               
               
                   
               
               
                 ggccgagctgtcggcctgcgtcatcacccagggggccatcctggcccaattgcaagccatccaga 
               
               
                   
               
               
                 aatcccgccaagaatttctgctgaaaaagggccacggggtctacttggacccccagaccggagag 
               
               
                   
               
               
                 gagctcaaccccagcttcccccaggatgccccgaggaagcagcaagaagctgaaagtggagctgc 
               
               
                   
               
               
                 cgccgccgccggaggatttggaggaagactgggagagcagtcaggcagaggaggaggagatggaa 
               
               
                   
               
               
                 gactgggacagcactcaggcagaggaggacagcctgcaagacagtctggaggaggaagacgaggt 
               
               
                   
               
               
                 ggaggaggcagaggaagaagcagccgccgccagaccgtcgtcctcggcggaggaggagaaagcaa 
               
               
                   
               
               
                 gcagcacggataccatctccgctccgggtcggggtcgcggcggccgggcccacagtagatgggac 
               
               
                   
               
               
                 gagaccgggcgcttcccgaaccccaccacccagaccggtaagaaggagcggcagggatacaagtc 
               
               
                   
               
               
                 ctggcgggggcacaaaaacgccatcgtctcctgcttgcaagcctgcgggggcaacatctccttca 
               
               
                   
               
               
                 cccggcgctacctgctcttccaccgcggggtgaacttcccccgcaacatcttgcattactaccgt 
               
               
                   
               
               
                 cacctccacagcccctactactgtttccaagaagaggcagaaacccagcagcagcagcagcagca 
               
               
                   
               
               
                 gaaaaccagcggcagcagctagaaaatccacagcggcggcaggtggactgaggatcgcggcgaac 
               
               
                   
               
               
                 gagccggcgcagacccgggagctgaggaaccggatctttcccaccctctatgccatcttccagca 
               
               
                   
               
               
                 gagtcgggggcaagagcaggaactgaaagtcaagaaccgttctctgcgctcgctcacccgcagtt 
               
               
                   
               
               
                 gtctgtatcacaagagcgaagaccaacttcagcgcactctcgaggacgccgaggctctcttcaac 
               
               
                   
               
               
                 aagtactgcgcgctcactcttaaagagtagcccgcgcccgcccacacacggaaaaaggcgggaat 
               
               
                   
               
               
                 tacgtcaccacctgcgcccttcgcccgaccatcatcatgagcaaagagattcccacgccttacat 
               
               
                   
               
               
                 gtggagctaccagccccagatgggcctggccgccggcgccgcccaggactactccacccgcatga 
               
               
                   
               
               
                 actggctcagtgccgggcccgcgatgatctcacgggtgaatgacatccgcgcccaccgaaaccag 
               
               
                   
               
               
                 atactcctagaacagtcagcgatcaccgccacgccccgccatcaccttaatccgcgtaattggcc 
               
               
                   
               
               
                 cgccgccctggtgtaccaggaaattccccagcccacgaccgtactacttccgcgagacgcccagg 
               
               
                   
               
               
                 ccgaagtccagctgactaactcaggtgtccagctggccggcggcgccgccctgtgtcgtcaccgc 
               
               
                   
               
               
                 cccgctcagggtataaagcggctggtgatccgaggcagaggcacacagctcaacgacgaggtggt 
               
               
                   
               
               
                 gagctcttcgctgggtctgcgacctgacggagtcttccaactcgccggatcggggagatcttcct 
               
               
                   
               
               
                 tcacgcctcgtcaggccgtcctgactttggagagttcgtcctcgcagccccgctcgggtggcatc 
               
               
                   
               
               
                 ggcactctccagttcgtggaggagttcactccctcggtctacttcaaccccttctccggctcccc 
               
               
                   
               
               
                 cggccactacccggacgagttcatcccgaacttcgacgccatcagcgagtcggtggacggctacg 
               
               
                   
               
               
                 attgaatgtcccatggtggcgcggctgacctagctcggcttcgacacctggaccactgccgccgc 
               
               
                   
               
               
                 ttccgctgcttcgctcgggatctcgccgagtttgcctactttgagctgcccgaggagcaccctca 
               
               
                   
               
               
                 gggcccggcccacggagtgcggatcgtcgtcgaagggggtctcgactcccacctgcttcggatct 
               
               
                   
               
               
                 tcagccagcgtccgatcctggccgagcgcgagcaaggacagacccttctgaccctgtactgcatc 
               
               
                   
               
               
                 tgcaaccaccccggcctgcatgaaagtctttgttgtctgctgtgtactgagtataataaaagctg 
               
               
                   
               
               
                 agatcagcgactactccggacttccgtgtgttcctgctatcaaccagtccctgttcttcaccggg 
               
               
                   
               
               
                 aacgagaccgagctccagctccagtgtaagccccacaagaagtacctcacctggctgttccaggg 
               
               
                   
               
               
                 ctctccgatcgccgttgtcaaccactgcgacaacgacggagtcctgctgagcggccctgccaacc 
               
               
                   
               
               
                 ttactttttccacccgcagaagcaagctccagctcttccaacccttcctccccgggacctatcag 
               
               
                   
               
               
                 tgcgtctcgggaccctgccatcacaccttccacctgatcccgaataccacagcgtcgctccccgc 
               
               
                   
               
               
                 tactaacaaccaaactacccaccaacgccaccgtcgcgaccgcggacatgtacagagctcgagaa 
               
               
                   
               
               
                 gtactaggccacaatacatgcccatattagactatgaggccgagccacagcgacccatgctcccc 
               
               
                   
               
               
                 gctattagttacttcaatctaaccggcggagatgactgacccactggccaacaacaacgtcaacg 
               
               
                   
               
               
                 accttctcctggacatggacggccgcgcctcggagcagcgactcgcccaacttcgcattcgccag 
               
               
                   
               
               
                 cagcaggagagagccgtcaaggagctgcaggacggcatagccatccaccagtgcaagaaaggcat 
               
               
                   
               
               
                 cttctgcctggtgaaacaggccaagatctcctacgaggtcaccccgaccgaccatcgcctctcct 
               
               
                   
               
               
                 acgagctcctgcagcagcgccagaagttcacctgcctggtcggagtcaaccccatcgtcatcacc 
               
               
                   
               
               
                 cagcagtcgggcgataccaaggggtgcatccactgctcctgcgactcccccgactgcgtccacac 
               
               
                   
               
               
                 tctgatcaagaccctctgcggcctccgcgacctcctccccatgaactaatcacccccttatccag 
               
               
                   
               
               
                 tgaaataaatatcatattgatgatgatttaaataaaaaataatcatttgatttgaaataaagata 
               
               
                   
               
               
                 caatcatattgatgatttgagttttaaaaaataaagaatcacttacttgaaatctgataccaggt 
               
               
                   
               
               
                 ctctgtccatgttttctgccaacaccacctcactcccctcttcccagctctggtactgcagaccc 
               
               
                   
               
               
                 cggcgggctgcaaacttcctccacacgctgaaggggatgtcaaattcctcctgtccctcaatctt 
               
               
                   
               
               
                 cattttatcttctatcagacccccccttcgtctcttcagatggattccaagagaagcccctgggg 
               
               
                   
               
               
                 gtgctgtccctgcgactggctgaccccgtcaccaccaagaacggggaaatcaccctcaagctggg 
               
               
                   
               
               
                 agagggggtggacctcgactcctcgggaaaactcatctccaacacggccaccaaggccgccgccc 
               
               
                   
               
               
                 ctctcagtttttccaacaacaccatttcccttaacatggatacccctctttataccaaagatgga 
               
               
                   
               
               
                 aaattatccttacaagtttctccaccgttaaacatattaaaatcaaccattctgaacacattagc 
               
               
                   
               
               
                 tgtagcttatggatcaggtttaggactgagtggtggcactgctcttgcagtacagttggcctctc 
               
               
                   
               
               
                 cactcacttttgatgaaaaaggaaatattaaaattaacctagccagtggtccattaacagttgat 
               
               
                   
               
               
                 gcaagtcgacttagtatcaactgcaaaagaggggtcactgtcactacctcaggagatgcaattga 
               
               
                   
               
               
                 aagcaacataagctggcctaaaggtataagatttgaaggtaatggcatagctgcaaacattggca 
               
               
                   
               
               
                 gaggattggaatttggaaccactagtacagagactgatgtcacagatgcatacccaattcaagtt 
               
               
                   
               
               
                 aaattgggtactggccttacctttgacagtacaggcgccattgttgcttggaacaaagaggatga 
               
               
                   
               
               
                 taaacttacattatggaccacagccgacccctcgccaaattgcaaaatatactctgaaaaagatg 
               
               
                   
               
               
                 ccaaactcacactttgcttgacaaagtgtggaagtcaaattctgggtactgtgactgtattggca 
               
               
                   
               
               
                 gtgaataatggaagtctcaacccaatcacaaacacagtaagcactgcactcgtctccctcaagtt 
               
               
                   
               
               
                 tgatgcaagtggagttttgctaagcagctccacattagacaaagaatattggaacttcagaaagg 
               
               
                   
               
               
                 gagatgttacacctgctgagccctatactaatgctataggttttatgcctaacataaaggcctat 
               
               
                   
               
               
                 cctaaaaacacatctgcagcttcaaaaagccatattgtcagtcaagtttatctcaatggggatga 
               
               
                   
               
               
                 ggccaaaccactgatgctgattattacttttaatgaaactgaggatgcaacttgcacctacagta 
               
               
                   
               
               
                 tcacttttcaatggaaatgggatagtactaagtacacaggtgaaacacttgctaccagctccttc 
               
               
                   
               
               
                 accttctcctacatcgcccaagaatgaacactgtatcccaccctgcataggattcgagcagttat 
               
               
                   
               
               
                 ttttcctccaccctcccaggacatggaatacaccaccctctccccccgcacagccttgaacatct 
               
               
                   
               
               
                 gaatgccattggtgatggacatgcttttggtctccacgttccacacagtttcagagcgagccagt 
               
               
                   
               
               
                 ctcgggtcggtcagggagatgaaaccctccgggcactcccgcatctgcacctcacagctcaacag 
               
               
                   
               
               
                 ctgaggattgtcctcggtggtcgggatcacggttatctggaagaagcagaagagcggcggtggga 
               
               
                   
               
               
                 atcatagtccgcgaacgggatcggccggtggtgtcgcatcaggccccgcagcagtcgctgccgcc 
               
               
                   
               
               
                 gccgctccgtcaagctgctgctcagggggtccgggtccagggactccctcagcatgatgcccacg 
               
               
                   
               
               
                 gccctcagcatcagtcgtctggtgcggcgggcgcagcagcgcatgcggatctcgctcaggtcgct 
               
               
                   
               
               
                 gcagtacgtgcaacacaggaccaccaggttgttcaacagtccatagttcaacacgctccagccga 
               
               
                   
               
               
                 aactcatcgcgggaaggatgctacccacgtggccgtcgtaccagatcctcaggtaaatcaagtgg 
               
               
                   
               
               
                 cgctccctccagaacacgctgcccacgtacatgatctccttgggcatgtggcggttcaccacctc 
               
               
                   
               
               
                 ccggtaccacatcaccctctggttgaacatgcagccccggatgatcctgcggaaccacagggcca 
               
               
                   
               
               
                 gcaccgccccgcccgccatgcagcgaagagaccccgggtcccggcaatggcaatggaggacccac 
               
               
                   
               
               
                 cgctcgtacccgtggatcatctgggagctgaacaagtctatgttggcacagcacaggcatatgct 
               
               
                   
               
               
                 catgcatctcttcagcactctcagctcctcgggggtcaaaaccatatcccagggcacggggaact 
               
               
                   
               
               
                 cttgcaggacagcgaaccccgcagaacagggcaatcctcgcacataacttacattgtgcatggac 
               
               
                   
               
               
                 agggtatcgcaatcaggcagcaccgggtgatcctccaccagagaagcgcgggtctcggtctcctc 
               
               
                   
               
               
                 acagcgtggtaagggggccggccgatacgggtgatggcgggacgcggctgatcgtgttcgcgacc 
               
               
                   
               
               
                 gtgtcatgatgcagttgctttcggacattttcgtacttgctgtagcagaacctggtccgggcgct 
               
               
                   
               
               
                 gcacaccgatcgccggcggcggtcccggcgcttggaacgctcggtgttgaaattgtaaaacagcc 
               
               
                   
               
               
                 actctctcagaccgtgcagcagatctagggcctcaggagtgatgaagatcccatcatgcctgata 
               
               
                   
               
               
                 gctctgatcacatcgaccaccgtggaatgggccagacccagccagatgatgcaattttgttgggt 
               
               
                   
               
               
                 ttcggtgacggcgggggagggaagaacaggaagaaccatgattaacttttaatccaaacggtctc 
               
               
                   
               
               
                 ggagcacttcaaaatgaaggtcgcggagatggcacctctcgcccccgctgtgttggtggaaaata 
               
               
                   
               
               
                 acagccaggtcaaaggtgatacggttctcgagatgttccacggtggcttccagcaaagcctccac 
               
               
                   
               
               
                 gcgcacatccagaaacaagacaatagcgaaagcgggagggttctctaattcctcaatcatcatgt 
               
               
                   
               
               
                 tacactcctgcaccatccccagataattttcatttttccagccttgaatgattcgaactagttcc 
               
               
                   
               
               
                 tgaggtaaatccaagccagccatgataaagagctcgcgcagagcgccctccaccggcattcttaa 
               
               
                   
               
               
                 gcacaccctcataattccaagatattctgctcctggttcacctgcagcagattgacaagcggaat 
               
               
                   
               
               
                 atcaaaatctctgccgcgatccctaagctcctccctcagcaataactgtaagtactctttcatat 
               
               
                   
               
               
                 cctctccgaaatttttagccataggaccaccaggaataagattagggcaagccacagtacagata 
               
               
                   
               
               
                 aaccgaagtcctccccagtgagcattgccaaatgcaagactgctataagcatgctggctagaccc 
               
               
                   
               
               
                 ggtgatatcttccagataactggacagaaaatcacccaggcaatttttaagaaaatcaacaaaag 
               
               
                   
               
               
                 aaaaatcctccaggtgcacgtttagagcctcgggaacaacgatgaagtaaatgcaagcggtgcgt 
               
               
                   
               
               
                 tccagcatggttagttagctgatctgtaaaaaacaaaaaataaaacattaaaccatgctagcctg 
               
               
                   
               
               
                 gcgaacaggtgggtaaatcgttctctccagcaccaggcaggccacggggtctccggcgcgaccct 
               
               
                   
               
               
                 cgtaaaaattgtcgctatgattgaaaaccatcacagagagacgttcccggtggccggcgtgaatg 
               
               
                   
               
               
                 attcgacaagatgaatacaccgatgccatgcggatgaagcacaaaatcctcaggtgcgtacaaaa 
               
               
                   
               
               
                 tgtaattactcccctcctgcacaggcagcgaagcccccgatccctccagatacacatacaaagcc 
               
               
                   
               
               
                 tcagcgtccatagcttaccgagcagcagcacacaacaggcgcaagagtcagagaaaggctgagct 
               
               
                   
               
               
                 ctaacctgtccacccgctctctgctcaatatatagcccagatctacactgacgtaaaggccaaag 
               
               
                   
               
               
                 tctaaaaatacccgccaaataatcacacacgcccagcacacgcccagaaaccggtgacacactca 
               
               
                   
               
               
                 aaaaaatacgcgcacttcctcaaacgcccaaactgccgtcatttccgggttcccacgctacgtca 
               
               
                   
               
               
                 tcggaattcgactttcaaattccgtcgaccgttaaaaacgtcacccgccccgcccctaacggtcg 
               
               
                   
               
               
                 cccgtctctcggccaatcaccttcctccctccccaaattcaaacagctcatttgcatattaacgc 
               
               
                   
               
               
                 gcaccaaaagtttgaggtatattattgatgatg 
               
            
           
         
       
     
     Example 6: Genetic Stability and Protein Expression 
     Genetic Stability: All of the vectors were genetically stable as determined by analyzing purified viral DNA by restriction enzyme digest followed by gel electrophoresis upon 12 sequential passages on HEK 293 cells. 
     Protein Expression: HEK 293 cells were infected for 48 hours with the different vectors. A cell lysate was prepared. Proteins were separated by SDS-PAGE. Bands spanning protein of approximate sizes from 110-160 kD was cut from the gel, protein were eluted and analyzed by Mass Spectrophotometry. The results (shown below) showed that for each of the cell lysates, peptides derived from gp140 could be detected. Sequences detected from the cell lysates within gp140 of the 3 different HIV clades expressed by the two adenoviral vector serotypes are underlined and in bold. The results indicated the AdC7 vector most likely only expresses low levels of the clade B gp140 protein. 
     
       
         
           
               
               
            
               
                 Gp140 Clade BC: Accession number, KC492738(SEQ ID NO: 4) 
                   
               
               
                 AdC6 gp140 BC 
               
               
                 (SEQ ID NO: 4) 
                   
               
               
                 MRVMGIRRNCQHLWRWGIMLLGMLMICSVVGNLWVTVYYGVPVWK   
                   
               
               
                   
               
               
                    AYDTEVHNVWATHACVPTDPNPQEMVLENVTENFNMWK   
               
               
                   
               
               
                    LTPLCVTLKCKNVSSNSTETPKLRGNSSETYKDEEMK 
               
               
                   
               
               
                 NCSFNATTILRDK  LDIAPLLLNSSENSSAYYSLINCNTSAIT 
               
               
                   
               
               
                 QACPKVSFDPIPIHYCTPAGYAILKCNDKKFNGTGPCSNVSTVQCTHGIKPV 
               
               
                   
               
               
                 VSTQLLLNGSLAEGEVIIRSKNLTDNAKTIIVQLNRSVEIVCTRPNNNTRKS 
               
               
                   
               
               
                 IRI  QAHCNISEDMWNETLHWVSRKLAEHFPNRTIN 
               
               
                   
               
               
                 FTSSSGGDLEIATHSFNCRGEFFYCNTSRLFNGTYMFNGTRGNSSSNSTITI 
               
               
                   
               
               
                 PCRIK  AMYAPPIEGNLTCRSNITGLLLVRDGGDNTNKTEIF 
               
               
                   
               
               
                 RPQGGDMRDNWRSELYKYK  LTVQAR 
               
               
                   
               
               
                    AIEAQQHLLQLTVWGIKQLQTRVLAIERYLK 
               
               
                   
               
               
                      LICTTAVPWNSSWSNKTQDEIWNNLTWMQWDKEISNYTD 
               
               
                   
               
               
                 TIYK    NEK  NLWSWFDITNWLW 
               
               
                   
               
               
                 AdC7 gp140 BC 
               
               
                 (SEQ ID NO: 4) 
                   
               
               
                 MRVMGIRRNCQHLWRWGIMLLGMLMICSVVGNLWVTVYYGVPVWK   
                   
               
               
                   
               
               
                    AYDTEVHNVWATHACVPTDPNPQEMVLENVTENFNMWK   
               
               
                   
               
               
                    LTPLCVTLKCKNVSSNSTETPKLRGNSSETYKDEEMKN 
               
               
                   
               
               
                 CSFNATTILRDKKQEVYALFYKLDIAPLLLNSSENSSAYYSLINCNTSAITQACPK 
               
               
                   
               
               
                 VSFDPIPIHYCTPAGYAILKCNDKKFNGTGPCSNVSTVQCTHGIKPVVSTQLLLNG 
               
               
                   
               
               
                 SLAEGEVIIRSKNLTDNAKTIIVQLNRSVEIVCTRPNNNTRKSIR 
               
               
                   
               
               
                    QAHCNISEDMWNETLHWVSRKLAEHFPNRTINFTSS 
               
               
                   
               
               
                 SGGDLEIATHSFNCRGEFFYCNTSRLFNGTYMFNGTRGNSSSNSTITIPCRIKQII 
               
               
                   
               
               
                 MWNQQVGRAMYAPPIEGNLTCRSNITGLLLVRDGGDNTNKTEIFRPQGGDMRDNWR 
               
               
                   
               
               
                 SELYKYK  LTVQAR   
               
               
                   
               
               
                 ATEAQQHLLQLTVWGIKQLQTRVLAIERYLKDQQLLGIWGCSGKLICTTAV 
               
               
                   
               
               
                 PWNSSWSNKTQDEIWNNLTWMQWDKEISNYTDTIYKLLEDSQNQQERNEKDLLAL 
               
               
                   
               
               
                 DSWKNLWSWFDITNWLW 
               
               
                   
               
               
                 Gp140 Clade B: Accession number, HM215399 (SEQ ID NO: 2) 
               
               
                 AdC6 GP140 B 
               
               
                 (SEQ ID NO: 2) 
                   
               
               
                 MRVKGIRKNYQHLWRWGTMLLGMLMICSAAENLWVTVYYGVPVWKEATTTLFCA 
                   
               
               
                   
               
               
                 SDAKAYDTEVHNIWATHACVPTDPNPQEVVLGNVTENFNMWKNDMVEQMHEDII 
               
               
                   
               
               
                 SLWDQSLKPCVKLTPLCVTLNCTNLRNTNNTSSNTSNMTEGGEIKNCSFDITTS 
               
               
                   
               
               
                 IRTKVKDYALFYELDIVAIDNTSYRLRQCNTSVITQACPK 
               
               
                   
               
               
                    LKCNNKTFNGTGPCTNVSTVQCTHRIRPVVSTQLLL 
               
               
                   
               
               
                 NGSLAEEEVVIRSSNFTDNAKVIIVQLKESVEINCTRPNNNTRKSIPLGPGKAW 
               
               
                   
               
               
                 YTTGQIIGDIRQAHCNLSRAK  KKLREQFGNKTIIFNQSSGGDPEV 
               
               
                   
               
               
                 VTHSFNCGGEFFYCNTSQLFNSTWYNNSTWNDTNDTTENSTITLPCRIKQIVNM 
               
               
                   
               
               
                 WQEVGKAMYAPPIRGQIRCSSNITGLLLTRDGGKNESNTTETFRPGGGDMRDNW 
               
               
                   
               
               
                 RSELYKYKVVK  AKLTVQAR    NLLR 
               
               
                   
               
               
                 AIEAQQHLLQLTVWGIKQLQARVLAVERYLKDQQLLGIWGCSGKLICTTAVPWN 
               
               
                   
               
               
                 VSWSNRSLSEIWDNMTWMEWEREIGNYTK     
               
               
                   
               
               
                 WASLWNWFNITNWLW 
               
               
                   
               
               
                 AdC7 GP140 B 
               
               
                 (SEQ ID NO: 2) 
                   
               
               
                 MRVKGIRKNYQHLWRWGTMLLGMLMICSAAENLWVTVYYGVPVWKEATTTLFCA 
                   
               
               
                   
               
               
                 SDAKAYDTEVHNIWATHACVPTDPNPQEVVLGNVTENFNMWKNDMVEQMHEDII 
               
               
                   
               
               
                 SLWDQSLKPCVKLTPLCVTLNCTNLRNTNNTSSNTSNMTEGGEIKNCSFDITTS 
               
               
                   
               
               
                 IRTKVKDYALFYELDIVAIDNTSYRLRQCNTSVITQACPKISFEPIPIHYCTPA 
               
               
                   
               
               
                 GFAILKCNNKTFNGTGPCTNVSTVQCTHRIRPVVSTQLLLNGSLAEEEVVIRSS 
               
               
                   
               
               
                 NFTDNAKVIIVQLKESVEINCTRPNNNTRKSIPLGPGKAWYTTGQIIGDIRQAH 
               
               
                   
               
               
                 CNLSRAKWENTLQQITKKLREQFGNKTIIFNQSSGGDPEVVTHSFNCGGEFFYC 
               
               
                   
               
               
                 NTSQLFNSTWYNNSTWNDTNDTTENSTITLPCRIKQIVNMWQEVGKAMYAPPIR 
               
               
                   
               
               
                 GQIRCSSNITGLLLTRDGGKNESNTTETFRPGGGDMRDNWRSELYKYKVVKIEP 
               
               
                   
               
               
                 LGVAPTRAKLTVQARQLLSGIVQQQRNLLRAIEAQQHLLQLTVWGIKQLQARVL 
               
               
                   
               
               
                 AVERYLKDQQLLGIWGCSGKLICTTAVPWNVSWSNRSLSEIWDNMTWMEWEREI 
               
               
                   
               
               
                 GNYTK  LELLEWDKWASLWNWFNITNWLW 
               
               
                   
               
               
                 Gp140 Clade C: Accession number, KF835515 (SEQ ID NO: 3) 
               
               
                 AdC6 GP140 C 
               
               
                 (SEQ ID NO: 3) 
                   
               
               
                 MRVRGTQRNYPQWWIWGILGFWMLMICNVGGNLWVTVYYGVPVWK   
                   
               
               
                   
               
               
                    AYENEVHNVWATHACVPTDPNPQEMVLENVTENFNMWK   
               
               
                   
               
               
                    TPLCVTLKCSNVTLKNNTVNSNETQYRKNCTFNTTT 
               
               
                   
               
               
                 ELKNRKQKVSAIFYRIDIVPLGNESSGNYRLINCNTSAITQACPKVSFDPIP 
               
               
                   
               
               
                 IHYCTPAGYALLKCNNKTFNGTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLA 
               
               
                   
               
               
                 EEEIIIRSENLTNNVKTIIVHLNESVEIVCIRPGNNTRQSIRI 
               
               
                   
               
               
                    QAHCNINGTKWNETLQGVGKKLAEHFPNKTIK 
               
               
                   
               
               
                    GEFFYCDTSGLFNSTYNSTYVPNGTESKPNITI 
               
               
                   
               
               
                 QCRIK  AMYAPPIKGSITCKSNITGLLLVRDGGANTTEEIFR 
               
               
                   
               
               
                 PGGGDMRDNVVRSELYKY  LTVQAR   
               
               
                   
               
               
                    AIEAQQHMLQLTVWGIKQLQTRVLAIERYLKDQQLLGIWGCSGKLICTT 
               
               
                   
               
               
                 AVPWNSSWSNKTQDEIWKNMTWMQWDREINNYTNTIYSLLEESQNQQEKNEK 
               
               
                   
               
               
                 D    NLWNWFDISNVVLW* 
               
               
                   
               
               
                 AdC7 GP140 C 
               
               
                 (SEQ ID NO: 3) 
                   
               
               
                 MRVRGTQRNYPQWWIWGILGFWMLMICNVGGNLWVTVYYGVPVWKEATTTLFCA 
                   
               
               
                   
               
               
                 SDAKAYENEVHNVWATHACVPTDPNPQEMVLENVTENFNMWKNEMVNQMHEDVI 
               
               
                   
               
               
                 SLWDQSLKPCVKLTPLCVTLKCSNVTLKNNTVNSNETQYRKNCTFNTTTELKNR 
               
               
                   
               
               
                 KQK  IDIVPLGNESSGNYRLINCNTSAITQACPKVSFDPIPIHYCTPA 
               
               
                   
               
               
                 GYALLKCNNKTFNGTGPCNNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSE 
               
               
                   
               
               
                 NLTNNVKTIIVHLNESVEIVCIRPGNNTRQSIRI  QAH 
               
               
                   
               
               
                 CNINGTKWNETLQGVGKKLAEHFPNKTIK  GEFFYC 
               
               
                   
               
               
                 DTSGLFNSTYNSTYVPNGTESKPNITIQCRIKQIINMWQEVGRAMYAPPIKGSI 
               
               
                   
               
               
                 TCKSNITGLLLVRDGGANTTEEIFRPGGGDMRDNWRSELYKYKVVEIKPLGIAP 
               
               
                   
               
               
                 TEAKLTVQAR  AIEAQQHMLQLTVWGIKQLQTRVLAIER 
               
               
                   
               
               
                 YLKDQQLLGIWGCSGKLICTTAVPWNSSWSNKTQDEIWKNMTWMQWDREINNYT 
               
               
                   
               
               
                 NTIYSLLEESQNQQEKNEKDLLALDSWKNLWNWFDISNWLW* 
               
               
                   
               
               
                 Gp140 Clade BC: Accession number, KC492738 (SEQ ID NO: 4) 
               
               
                 AdC6 GP140 BC 
               
               
                 (SEQ ID NO: 4) 
                   
               
               
                 MRVMGIRRNCQHLWRWGIMLLGMLMICSVVGNLWVTVYYGVPVWK   
                   
               
               
                   
               
               
                    AYDTEVHNVWATHACVPTDPNPQEMVLENVTENFNMWK   
               
               
                   
               
               
                    LTPLCVTLKCKNVSSNSTETPKLRGNSSETYKDEEMK 
               
               
                   
               
               
                 NCSFNATTILRDKK  LDIAPLLLNSSENSSAYYSLINCNTSAIT 
               
               
                   
               
               
                 QACPKVSFDPIPIHYCTPAGYAILKCNDKKFNGTGPCSNVSTVQCTHGIKPV 
               
               
                   
               
               
                 VSTQLLLNGSLAEGEVIIRSKNLTDNAKTIIVQLNRSVEIVCTRPNNNTRKS 
               
               
                   
               
               
                 IR  QAHCNISEDMWNETLHWVSRKLAEHFPNRTIN 
               
               
                   
               
               
                 FTSSSGGDLEIATHSFNCRGEFFYCNTSRLFNGTYMFNGTRGNSSSNSTITI 
               
               
                   
               
               
                 PCRIK  AMYAPPIEGNLTCRSNITGLLLVRDGGDNTNKTEIF 
               
               
                   
               
               
                 RPQGGDMRDNWRSELYKYK  LTVQAR 
               
               
                   
               
               
                    AIEAQQHLLQLTVWGIKQLQTRVLAIERYLK 
               
               
                   
               
               
                      LICTTAVPWNSSWSNKTQDEIWNNLTWMQWDKEISNYTD 
               
               
                   
               
               
                 TIYK    NEK  NLWSWFDITNWLW* 
               
               
                   
               
               
                 AdC7 GP140 BC 
               
               
                 (SEQ ID NO: 4) 
                   
               
               
                 MRVMGIRRNCQHLWRWGIMLLGMLMICSVVGNLWVTVYYGVPVWK   
                   
               
               
                   
               
               
                    AYDTEVHNVWATHACVPTDPNPQEMVLENVTENFNMWK   
               
               
                   
               
               
                    LTPLCVTLKCKNVSSNSTETPKLRGNSSETYKDEEMK 
               
               
                   
               
               
                 NCSFNATTILRDKK  LDIAPLLLNSSENSSAYYSLINCNTSAIT 
               
               
                   
               
               
                 QACPKVSFDPIPIHYCTPAGYAILKCNDKKFNGTGPCSNVSTVQCTHGIKPV 
               
               
                   
               
               
                 VSTQLLLNGSLAEGEVIIRSKNLTDNAKTIIVQLNRSVEIVCTRPNNNTRKS 
               
               
                   
               
               
                 IR  QAHCNISEDMWNETLHWVSRKLAEHFPNRTIN 
               
               
                   
               
               
                 FTSSSGGDLEIATHSFNCRGEFFYCNTSRLFNGTYMFNGTRGNSSSNSTITI 
               
               
                   
               
               
                 PCRIKQIINMWQQVGRAMYAPPIEGNLTCRSNITGLLLVRDGGDNTNKTEIF 
               
               
                   
               
               
                 RPQGGDMRDNWRSELYKYK  LTVQAR 
               
               
                   
               
               
                    AIEAQQHLLQLTVWGIKQLQTRVLAIERYLKDQQLLG 
               
               
                   
               
               
                 IWGCSGKLICTTAVPWNSSWSNKTQDEIWNNLTWMQWDKEISNYTDTIYKLL 
               
               
                   
               
               
                 EDSQNQQERNEKDLLALDSWKNLWSWFDITNWLW 
               
            
           
         
       
     
     REFERENCES 
     
         
         Carnathan D G, Wetzel K S, Yu J, Lee S T, Johnson B A, Paiardini M, Yan J, Morrow M P, Sardesai N Y, Weiner D B, Ertl H C, Silvestri G.  Activated CD 4 +CCR 5 + T cells in the rectum predict increased SIV acquisition in SIVGag/Tat - vaccinated rhesus macaques . Proc Natl Acad Sci USA. 2015 Jan. 13; 112(2):518-23. 
         Tuyishime S, Haut L H, Kurupati R K, Billingsley J M, Carnathan D, Gangahara S, Styles T M, Xiang Z, Li Y, Zopfs M, Liu Q, Zhou X, Lewis M G,  Amara  RR, Bosinger S, Silvestri G, Ertl H C J.  Correlates of Protection Against SIV   mac251    Infection in Rhesus Macaques Immunized With Chimpanzee - Derived Adenovirus Vectors . EBioMedicine. 2018 May; 31:25-35. 
         Cervasi B, Carnathan D G, Sheehan K M, Micci L, Paiardini M, Kurupati R, Tuyishime S, Zhou X Y, Else J G, Ratcliffe S J, Ertl H C, Silvestri G.  Immunological and virological analyses of rhesus macaques immunized with chimpanzee adenoviruses expressing the simian immunodeficiency virus Gag/Tat fusion protein and challenged intrarectally with repeated low doses of SIVmac . J Virol. 2013 September; 87(17):9420-30. 
         Lasaro M O, Haut L H, Zhou X, Xiang Z, Zhou D, Li Y, Giles-Davis W, Li H, Engram J C, Dimenna L J, Bian A, Sazanovich M, Parzych E M, Kurupati R, Small J C, Wu T L, Leskowitz R M, Klatt N R, Brenchley J M, Garber D A, Lewis M, Ratcliffe S J, Betts M R, Silvestri G, Ertl H C.  Vaccine - induced T cells provide partial protection against high - dose rectal SIVmac 239  challenge of rhesus macaques . Mol Ther. 2011 February; 19(2):417-26. 
         Tatsis N, Lasaro M O, Lin S W, Haut L H, Xiang Z Q, Zhou D, Dimenna L, Li H, Bian A, Abdulla S, Li Y, Giles-Davis W, Engram J, Ratcliffe S J, Silvestri G, Ertl H C, Betts M R.  Adenovirus vector - induced immune responses in nonhuman primates: responses to prime boost regimens . J Immunol. 2009 May 15; 182(10):6587-99. 
       
    
     Other Embodiments 
     The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. 
     While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations and subcombinations.