Patent Publication Number: US-2020276297-A1

Title: Vaccines and methods of making and using vaccines for prevention of respiratory syncytial virus (rsv) infections

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims benefit of U.S. Provisional Application No. 62/559,167, filed Sep. 15, 2017, which is incorporated herein by reference in its entirety. 
    
    
     BACKGROUND 
     A global study has found that RSV is one of the most common causes of infant hospitalization due to acute lower respiratory tract infections (ALRI) in children younger than 5 years of age in the US and worldwide, resulting in up to 200,000 deaths. RSV was associated with hospitalizations 16-times more than influenza in children under one year of age. In addition to hospitalization, RSV resulted in higher rates of emergency department visits and required more caregiver time and resource utilization than influenza. 
     Currently, several RSV vaccine candidates are under development or clinical trials targeting different age groups. Both live attenuated and killed vaccines have been attempted, but without much success. Recombinant viral vectors, such as recombinant vesicular stomatitis virus (rVSV), adenovirus, etc., provide powerful technologies for delivering heterologous antigens (antigens from different viruses) with minimal disadvantages. What is needed in the art is an efficacious rVSV vector based anti-RSV vaccine that safely used in humans to prevent RSV infections. 
     SUMMARY 
     Disclosed herein are compositions comprising a recombinant viral vector and one or more respiratory syncytial virus (RSV) proteins. 
     Also disclosed herein are methods of using the immunogenic compositions and vaccines disclosed herein. For example, disclosed are methods of eliciting an immune response against RSV in a subject, the method comprising administering to the subject a composition or vaccine as disclosed herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a schematic representation of the VSV vector (Indiana strain; sequence listed as the last sequence in the list of sequences) with the location for cloning of the RSV genes. 
         FIGS. 2A, 2B, and 2C  show clearance of challenge virus (a and b) and VN antibody titers (c) in the rVSV-G±F immunized cotton rats. Cotton rats (n=4 per group) were immunized with indicated dose and combination of the rVSV candidates and challenged with RSV-A2 four weeks after immunization and euthanized four days after challenge. Virus titration was done using lung and nasal homogenates collected on the day of euthanization and VN antibody levels were determined from the serum samples collected on the day of challenge. Statistical analysis was done by one-way ANOVA and statistically significant difference (at P&lt;0.05) between indicated group representing bars is indicated by asterisk (*) symbol. 
         FIGS. 3A, 3B, and 3C  show clearance of challenge virus (a and b) and VN antibody titers (c) in the rVSV-G±F immunized cotton rats. Cotton rats (n=4 per group) were immunized with indicated dose, interval and combination of the rVSV candidates and challenged with RSV-A2 three weeks after booster dose and euthanized four days after challenge. Virus titration was done using lung and nasal homogenates and VN antibody levels were determined from the serum samples collected on the day of booster immunization (day 21) and RSV challenge (day 42). Statistical analysis was done by one-way ANOVA and statistically significant difference (at P&lt;0.05) between indicated groups representing bars is indicated by asterisk (*) symbol. 
         FIGS. 4A, 4B, and 4C  show clearance of challenge virus (a and b) and VN antibody titers (c) in the indicated rVSV-G+F+rVSV-Hsp70 immunized cotton rats. Cotton rats (n=4 per group) were immunized with indicated dose, interval and combination of the rVSV candidates and challenged with RSV-A2 three weeks after booster dose and euthanized four days after challenge. Virus titration was done using lung and nasal homogenates and VN antibody levels were determined from the serum samples collected on the day of booster immunization (day 21) and RSV challenge (day 42). Statistical analysis was done by one-way ANOVA and statistically significant difference (at P&lt;0.05) between indicated groups representing bars is indicated by asterisk (*) symbol. 
         FIGS. 5A, 5B, 5C  show clearance of challenge virus (a and b) and VN antibody titers (c) in the indicated variant of RSV G expressing rVSV immunized cotton rats. Cotton rats (n=4 per group) were immunized with indicated dose, interval and combination of the rVSV candidates and challenged with RSV-A2 three weeks after booster dose and euthanized four days after challenge. Virus titration was done using lung and nasal homogenates and VN antibody levels were determined from the serum samples collected on the day of booster immunization (day 21) and RSV challenge (day 42). Statistical analysis was done by one-way ANOVA and statistically significant difference (at P&lt;0.05) between indicated groups representing bars is indicated by asterisk (*) symbol. 
         FIGS. 6A, 6B, and 6C  show clearance of challenge virus (a and b) and VN antibody titers (c) in the rVSV-G variants immunized cotton rats. Cotton rats (n=4 per group) were immunized with indicated dose and combination of the rVSV candidates and challenged with RSV-A2 after four weeks and euthanized four days after challenge. Virus titration was done using lung and nasal homogenates and VN antibody levels were determined from the serum samples collected on the day of challenge. Statistical analysis was done by one-way ANOVA and statistically significant difference (at P&lt;0.05) between indicated group representing bars is indicated by asterisk (*) symbol. 
         FIG. 7  shows a schematic representation of the ectodomain of the RSV F gene with details of the mutations and substitutions included to stabilize F protein in perfusion conformation (Pre-F). 
         FIG. 8  shows a schematic representation of RSV N gene and segments of the gene selected for expression in rVSVs vectors as detailed in Table. 3. 
     
    
    
     DETAILED DESCRIPTION 
     The present invention can be understood more readily by reference to the following detailed description of the invention and the Examples included therein. 
     All patents, patent applications, and publications cited herein, whether supra or infra, are hereby incorporated by reference in their entireties into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. 
     Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is in no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. 
     Definitions 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The terminology used in the description of the embodiments herein is for describing particular embodiments only and is not intended to be limiting of the embodiments disclosed. As used in the description, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. 
     Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in this disclosure are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in this disclosure are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches. 
     Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values described herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “10” is disclosed the “less than or equal to 10” as well as “greater than or equal to 10” is also disclosed. It is also understood that throughout the application, data are provided in a number of different formats, and that these data, represent endpoints, starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. 
     As used herein, the term “amino acid sequence” refers to a list of abbreviations, letters, characters or words representing amino acid residues. The amino acid abbreviations used herein are conventional one letter codes for the amino acids and are expressed as follows: A, alanine; C, cysteine; D aspartic acid; E, glutamic acid; F, phenylalanine; G, glycine; H histidine; I isoleucine; K, lysine; L, leucine; M, methionine; N, asparagine; P, proline; Q, glutamine; R, arginine; S, serine; T, threonine; V, valine; W, tryptophan; Y, tyrosine. 
     “Polypeptide” as used herein refers to any peptide, oligopeptide, polypeptide, gene product, expression product, or protein. A polypeptide is comprised of consecutive amino acids. The term “polypeptide” encompasses naturally occurring or synthetic molecules. The terms “polypeptide,” “peptide,” and “protein” can be used interchangeably. 
     In addition, as used herein, the term “polypeptide” refers to amino acids joined to each other by peptide bonds or modified peptide bonds, e.g., peptide isosteres, etc. and may contain modified amino acids other than the 20 gene-encoded amino acids. The polypeptides can be modified by either natural processes, such as post-translational processing, or by chemical modification techniques which are well known in the art. Modifications can occur anywhere in the polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. The same type of modification can be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide can have many types of modifications. Modifications include, without limitation, acetylation, acylation, ADP-ribosylation, amidation, covalent cross-linking or cyclization, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of a phosphytidylinositol, disulfide bond formation, demethylation, formation of cysteine or pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristolyation, oxidation, pergylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, and transfer-RNA mediated addition of amino acids to protein such as arginylation. (See Proteins—Structure and Molecular Properties 2nd Ed., T. E. Creighton, W.H. Freeman and Company, New York (1993); Posttranslational Covalent Modification of Proteins, B. C. Johnson, Ed., Academic Press, New York, pp. 1-12 (1983)). 
     As used herein, “isolated polypeptide” or “purified polypeptide” is meant to mean a polypeptide (or a fragment thereof) that is substantially free from the materials with which the polypeptide is normally associated in nature. The polypeptides of the invention, or fragments thereof, can be obtained, for example, by extraction from a natural source (for example, a mammalian cell), by expression of a recombinant nucleic acid encoding the polypeptide (for example, in a cell or in a cell-free translation system), or by chemically synthesizing the polypeptide. In addition, polypeptide fragments may be obtained by any of these methods, or by cleaving full length proteins and/or polypeptides. 
     The phrase “nucleic acid” as used herein refers to a naturally occurring or synthetic oligonucleotide or polynucleotide, whether DNA or RNA or DNA-RNA hybrid, single-stranded or double-stranded, sense or antisense, which is capable of hybridization to a complementary nucleic acid by Watson-Crick base-pairing. Nucleic acids of the invention can also include nucleotide analogs (e.g., BrdU), and non-phosphodiester internucleoside linkages (e.g., peptide nucleic acid (PNA) or thiodiester linkages). In particular, nucleic acids can include, without limitation, DNA, RNA, cDNA, gDNA, ssDNA, dsDNA or any combination thereof. 
     As used herein, “isolated nucleic acid” or “purified nucleic acid” is meant to mean DNA that is free of the genes that, in the naturally-occurring genome of the organism from which the DNA of the invention is derived, flank the gene. The term therefore includes, for example, a recombinant DNA which is incorporated into a vector, such as an autonomously replicating plasmid or virus; or incorporated into the genomic DNA of a prokaryote or eukaryote (e.g., a transgene); or which exists as a separate molecule (for example, a cDNA or a genomic or cDNA fragment produced by PCR, restriction endonuclease digestion, or chemical or in vitro synthesis). It also includes a recombinant DNA which is part of a hybrid gene encoding additional polypeptide sequence. The term “isolated nucleic acid” also refers to RNA, e.g., an mRNA molecule that is encoded by an isolated DNA molecule, or that is chemically synthesized, or that is separated or substantially free from at least some cellular components, for example, other types of RNA molecules or polypeptide molecules. 
     As used herein, “sample” is meant to mean an animal; a tissue or organ from an animal; a cell (either within a subject, taken directly from a subject, or a cell maintained in culture or from a cultured cell line); a cell lysate (or lysate fraction) or cell extract; or a solution containing one or more molecules derived from a cell or cellular material (e.g. a polypeptide or nucleic acid), which is assayed as described herein. A sample can also be any body fluid or excretion (for example, but not limited to, blood, urine, stool, saliva, tears, bile) that contains cells or cell components. 
     Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The term “comprises” means “includes.” Thus, unless the context requires otherwise, the word “comprises,” and variations such as “comprise” and “comprising” will be understood to imply the inclusion of a stated compound or composition (e.g., nucleic acid, polypeptide, antigen) or step, or group of compounds or steps, but not to the exclusion of any other compounds, composition, steps, or groups thereof. 
     An “immunogenic composition” is a composition of matter suitable for administration to a human or animal subject (e.g., in an experimental setting) that is capable of eliciting a specific immune response, e.g., against a pathogen, such as RSV. As such, an immunogenic composition includes one or more antigens (for example, whole purified virus or antigenic subunits, e.g., polypeptides, thereof) or antigenic epitopes. An immunogenic composition can also include one or more additional components capable of eliciting or enhancing an immune response, such as an excipient, carrier, and/or adjuvant. In certain instances, immunogenic compositions are administered to elicit an immune response that protects the subject against symptoms or conditions induced by a pathogen. In some cases, symptoms or disease caused by a pathogen is prevented (or treated, e.g., reduced or ameliorated) by inhibiting replication of the pathogen following exposure of the subject to the pathogen. In the context of this disclosure, the term immunogenic composition will be understood to encompass compositions that are intended for administration to a subject or population of subjects for the purpose of eliciting a protective or palliative immune response against the virus (that is, vaccine compositions or vaccines). 
     The term “purification” (e.g., with respect to a pathogen or a composition containing a pathogen) refers to the process of removing components from a composition, the presence of which is not desired. Purification is a relative term, and does not require that all traces of the undesirable component be removed from the composition. In the context of vaccine production, purification includes such processes as centrifugation, dialization, ion-exchange chromatography, and size-exclusion chromatography, affinity-purification or precipitation. Thus, the term “purified” does not require absolute purity; rather, it is intended as a relative term. Thus, for example, a purified virus preparation is one in which the virus is more enriched than it is in its generative environment, for instance within a cell or population of cells in which it is replicated naturally or in an artificial environment. A preparation of substantially pure viruses can be purified such that the desired virus or viral component represents at least 50% of the total protein content of the preparation. In certain embodiments, a substantially pure virus will represent at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, or at least 95% or more of the total protein content of the preparation. 
     An “isolated” biological component (such as a virus, nucleic acid molecule, protein or organelle) has been substantially separated or purified away from other biological components in the cell and/or organism in which the component occurs or is produced. Viruses and viral components, e.g., proteins, which have been “isolated” include viruses, and proteins, purified by standard purification methods. The term also embraces viruses and viral components (such as viral proteins) prepared by recombinant expression in a host cell. 
     An “antigen” is a compound, composition, or substance that can stimulate the production of antibodies and/or a T cell response in an animal, including compositions that are injected, absorbed or otherwise introduced into an animal. The term “antigen” includes all related antigenic epitopes. The term “epitope” or “antigenic determinant” refers to a site on an antigen to which B and/or T cells respond. The “dominant antigenic epitopes” or “dominant epitope” are those epitopes to which a functionally significant host immune response, e.g., an antibody response or a T-cell response, is made. Thus, with respect to a protective immune response against a pathogen, the dominant antigenic epitopes are those antigenic moieties that when recognized by the host immune system result in protection from disease caused by the pathogen. The term “T-cell epitope” refers to an epitope that when bound to an appropriate MHC molecule is specifically bound by a T cell (via a T cell receptor). A “B-cell epitope” is an epitope that is specifically bound by an antibody (or B cell receptor molecule). An antigen can also affect the innate immune response. 
     An “immune response” is a response of a cell of the immune system, such as a B cell, T cell, or monocyte, to a stimulus. An immune response can be a B cell response, which results in the production of specific antibodies, such as antigen specific neutralizing antibodies. An immune response can also be a T cell response, such as a CD4+ response or a CD8+ response. In some cases, the response is specific for a particular antigen (that is, an “antigen-specific response”). An immune response can also include the innate response. If the antigen is derived from a pathogen, the antigen-specific response is a “pathogen-specific response.” A “protective immune response” is an immune response that inhibits a detrimental function or activity of a pathogen, reduces infection by a pathogen, or decreases symptoms (including death) that result from infection by the pathogen. A protective immune response can be measured, for example, by the inhibition of viral replication or plaque formation in a plaque reduction assay or ELISA-neutralization assay, or by measuring resistance to pathogen challenge in vivo. 
     The immunogenic compositions disclosed herein are suitable for preventing, ameliorating and/or treating disease caused by infection of the virus. 
     By “reduce” or other forms of the word, such as “reducing” or “reduction,” is meant lowering of an event or characteristic (e.g., viral infection). It is understood that this is typically in relation to some standard or expected value, in other words it is relative, but that it is not always necessary for the standard or relative value to be referred to. For example, “reduces viral infection” means decreasing the amount of virus relative to a standard or a control. 
     By “prevent” or other forms of the word, such as “preventing” or “prevention,” is meant to stop a particular event or characteristic, to stabilize or delay the development or progression of a particular event or characteristic, or to minimize the chances that a particular event or characteristic will occur. Prevent does not require comparison to a control as it is typically more absolute than, for example, reduce. As used herein, something could be reduced but not prevented, but something that is reduced could also be prevented. Likewise, something could be prevented but not reduced, but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless specifically indicated otherwise, the use of the other word is also expressly disclosed. 
     As used herein, “treatment” refers to obtaining beneficial or desired clinical results. Beneficial or desired clinical results include, but are not limited to, any one or more of: alleviation of one or more symptoms (such as infection), diminishment of extent of infection, stabilized (i.e., not worsening) state of infection, preventing or delaying spread of the infection, preventing or delaying occurrence or recurrence of infection, and delay or slowing of infection progression. 
     The term “patient” preferably refers to a human in need of treatment with an antibiotic or treatment for any purpose, and more preferably a human in need of such a treatment to treat viral infection. However, the term “patient” can also refer to non-human animals, preferably mammals such as dogs, cats, horses, cows, pigs, sheep and non-human primates, among others, that are in need of treatment with antibiotics. 
     Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein. 
     In addition, where features or aspects of the inventions are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group. 
     General Description 
     RSV has four major structural proteins (glycoprotein [G], fusion [F] protein, Nucleoprotein [N] and M 2-1 ) which are responsible for induction of humoral and cell mediated immune responses in the infected individual. Humoral (or antibody mediated) immunity is required for neutralizing/limiting the virus spread, whereas, cell mediated immunity is required for clearance of the virus from the body of the infected individual. G and F are surface proteins and induce both neutralizing antibodies and T cell mediated immune responses. N and M 2-1  are internal proteins and contribute in induction of T cell response. 
     Four types of recombinant VSVs have been developed, each individually expressing one of the four above mentioned antigenic structural proteins (modified or unmodified) between glycoprotein (G) and polymerase (L) protein genes of the rVSV vector ( FIG. 1 ). For expression of G protein, in addition to the cloning of wildtype G protein gene in the rVSV, a codon optimized version of the gene has been cloned. Codon optimization of a gene enables higher expression of the vaccine antigen (G protein, in this case). Therefore, from the same dose of the vaccine, a codon optimized gene expressing VSV produces significantly higher levels of the antigen protein resulting in dose amplification, so that the required dose of the rVSV can be significantly reduced. Further, in the context of RSV infection, G protein is produced in two forms (membrane bound [mG] and secretory [sG] forms). rVSVs expressing both forms have been produced. Further, RSV-G protein has been cloned with (Table 1) and pre-clinical in vivo efficacy studies have been conducted in the cotton rat animal model. 
     It is noted that viruses other than RSV can be used with the rVSV platforms disclosed herein. Examples of other viruses are known to those of skill in the art and include other respiratory (human and animal) viruses such as, human metapneumo virus, influenza, and bRSV. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 S. 
                 Name of the 
                 Characteristic of the RSV 
                 Rationale for expression in the 
               
               
                 No. 
                 recombinant 
                 G protein 
                 rVSV vector 
               
               
                   
               
             
            
               
                 1 
                 rVSV-G 
                 Wildtype RSV-G protein 
                 G protein is the receptor binding 
               
               
                   
                   
                   
                 ligand of the RSV and immunogenic 
               
               
                   
                   
                   
                 because of presence of antigenic 
               
               
                   
                   
                   
                 epitopes 
               
               
                 2 
                 rVSV-cG 
                 Codon-optimized RSV- G 
                 Codon optimization enhances 
               
               
                   
                   
                 protein (full length with 298 
                 expression of the G protein resulting 
               
               
                   
                   
                 amino acid [AA] length). 
                 in dose sparing/amplification effect. 
               
               
                 3 
                 rVSV-mG 
                 Codon-optimized RSV- G 
                 Membrane bound G protein is more 
               
               
                   
                   
                 protein stabilized to express 
                 immunogenic than secretory G 
               
               
                   
                   
                 only membrane bound form 
                 protein. 
               
               
                   
                   
                 by mutating second start 
               
               
                   
                   
                 codon at amino acid (AA) 
               
               
                   
                   
                 position 48, from Methionine 
               
               
                   
                   
                 to Isoleucine (M48I). 
               
               
                 4 
                 rVSV-G 
                 Codon-optimized RSV- G 
                 Expected to be attenuated because of 
               
               
                   
                 (C186S) 
                 protein with disrupted 
                 the disrupted receptor binding 
               
               
                   
                   
                 receptor binding domain, 
                 domain and possibly increasing the 
               
               
                   
                   
                 CX3C motif, in the ‘cysteine 
                 immunogenicity of the G protein. 
               
               
                   
                   
                 noose’ of the central 
               
               
                   
                   
                 conserved domain of the G 
               
               
                   
                   
                 protein. 
               
               
                 5 
                 rVSV- SecG 
                 Codon-optimized 250 AA 
                 To elucidate the purported role of 
               
               
                   
                   
                 sized mRSV- G (starting 
                 Sec-G as ‘decoy’ antigen 
               
               
                   
                   
                 from second start codon at 
               
               
                   
                   
                 AA position 48/with 
               
               
                   
                   
                 truncated cytoplasmic tail 
               
               
                   
                   
                 and part of the 
               
               
                   
                   
                 transmembrane domain) 
               
               
                 6 
                 rVSV-GΔNg 
                 Codon optimized RSV- G 
                 Few reports have shown that 
               
               
                   
                   
                 protein with deletion of five 
                 unglycosylated/prokaryotically 
               
               
                   
                   
                 putative N-glycosylation 
                 expressed G protein was more 
               
               
                   
                   
                 sites by mutation of 
                 immunogenic than glycosylated form. 
               
               
                   
                   
                 Aspargine residue to alanine. 
               
               
                 7 
                 rVSV- 
                 Codon optimized ‘membrane 
                 We predicted that membrane-bound 
               
               
                   
                 mGΔNg 
                 bound’ RSV- G protein (as 
                 partially unglycosylated G is more 
               
               
                   
                   
                 in rVSV-mG) with deletion 
                 immunogenic than rVSV-GΔNg 
               
               
                   
                   
                 of five putative N- 
               
               
                   
                   
                 glycosylation sites by 
               
               
                   
                   
                 mutation of Aspargine 
               
               
                   
                   
                 residue to alanine. 
               
               
                 8 
                 rVSV-G 
                 28 AA long peptide 
                 Shown to be immunogenic in other 
               
               
                   
                 (aa163-190) 
                 comprising of ‘central 
                 expression systems as it compasses 
               
               
                   
                   
                 conserved domain’ of the G 
                 the most conserved region of the G 
               
               
                   
                   
                 protein 
                 protein including receptor binding 
               
               
                   
                   
                   
                 CX3C motif 
               
               
                 9 
                 rVSV-G 
                 101 AA long peptide 
                 Shown to be immunogenic in other 
               
               
                   
                 (aa130-230) 
                 comprising of ‘central 
                 expression systems as it compasses 
               
               
                   
                   
                 conserved domain’ of the G 
                 the most conserved region of the G 
               
               
                   
                   
                 protein 
                 protein including receptor binding 
               
               
                   
                   
                   
                 CX3C motif 
               
               
                   
               
            
           
         
       
     
     RSV F protein is involved in the fusion of the virus to the cell membrane of the infected cell and has a higher number of neutralizing epitopes, antigenic sites and T-cell epitopes than G protein, thus, making it an attractive vaccine candidate. F protein exists in two different structural conformations, pre-fusion and post-fusion (Pre-F and Post-F), and Pre-F has been shown to be more immunogenic than Post-F. Therefore, wildtype F and Pre-F genes have been cloned in rVSV (Table 2). The codon-optimized F gene in rVSV can also be cloned. Disclosed herein are various formats of F-protein, including codon-optimized F protein, pre-fusion conformation stabilized F-protein, and post-fusion F protein. The F protein can be wildtype or codon-optimized. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 S. 
                 Name of the 
                 Characteristic of the RSV 
                 Rationale for expression in the 
               
               
                 No. 
                 recombinant 
                 F protein 
                 rVSV vector 
               
               
                   
               
             
            
               
                 1 
                 rVSV-F 
                 Wildtype RSV-F protein 
                 F protein is responsible for the fusion 
               
               
                   
                   
                   
                 of the virus with host cell and has 
               
               
                   
                   
                   
                 more number of neutralizing and 
               
               
                   
                   
                   
                 CTL epitopes. 
               
               
                 2 
                 rVSV-Pre-F- 
                 Codon-optimized RSV- F 
                 Codon optimization enhances 
               
               
                   
                 Foldon 
                 protein with mutations in the 
                 expression of the F protein resulting 
               
               
                   
                   
                 F gene leading to stabilizing 
                 in dose sparing/amplification effect. 
               
               
                   
                   
                 the protein in Pre-F 
                 Further, stabilization of the 
               
               
                   
                   
                 conformation. 
                 conformation in pre-fusion state 
               
               
                   
                   
                   
                 enables it to induce highly protective 
               
               
                   
                   
                   
                 immune response. 
               
               
                 3 
                 rVSV-Pre-F 
                 Codon-optimized full-length 
                 Codon optimization enhances 
               
               
                   
                   
                 RSV- F protein with 
                 expression of the F protein resulting 
               
               
                   
                   
                 mutations in the F gene 
                 in dose sparing/amplification effect. 
               
               
                   
                   
                 leading to stabilizing the 
                 Further, stabilization of the 
               
               
                   
                   
                 protein in Pre-F 
                 conformation in pre-fusion state 
               
               
                   
                   
                 conformation. 
                 enables it to induce highly protective 
               
               
                   
                   
                   
                 immune response. 
               
               
                 4 
                 rVSV-Post F 
                 Codon-optimized RSV- F 
                 Post-fusion F protein is shown to 
               
               
                   
                   
                 protein ectodomain 
                 induce protective immunity in few 
               
               
                   
                   
                 conformation. 
                 studies. 
               
               
                 5 
                 rVSV-HEK- 
                 Codon-optimized full-length 
                 Codon optimization enhances 
               
               
                   
                 Pre-F 
                 RSV- F protein with 
                 expression of the F protein resulting 
               
               
                   
                   
                 mutations in the F gene 
                 in dose sparing/amplification effect. 
               
               
                   
                   
                 leading to stabilizing the 
                 Further, stabilization of the 
               
               
                   
                   
                 protein in Pre-F 
                 conformation in pre-fusion state 
               
               
                   
                   
                 conformation with HEK 
                 enables it to induce highly protective 
               
               
                   
                   
                 assignments. 
                 immune response. 
               
               
                   
               
            
           
         
       
     
     Further, N and M 2-1  proteins have been shown to contain several putative sites of T-cell epitopes inducing cell mediated immunity, which is responsible for clearance of the infective RSV virus from the body. Therefore, rVSVs expressing M 2-1  and different segments of the N gene have been cloned and recovered (Table 3). 
     
       
         
           
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 S. 
                 Name of the 
                 Characteristic of the RSV 
                 Rationale for expression in the 
               
               
                 No. 
                 recombinant 
                 N or M2-1 protein 
                 rVSV vector 
               
               
                   
               
             
            
               
                 1 
                 rVSV-NΔ3 
                 238 AA length amino terminal 
                 Comprises of two putative T-cell 
               
               
                   
                   
                 domain (NTD) of the N protein 
                 epitopes 
               
               
                 2 
                 rVSV-NΔ3-l 
                 254 AA length NTD and 16 AA 
                 Comprises of five putative T-cell 
               
               
                   
                   
                 of the carboxylic terminal 
                 epitopes 
               
               
                   
                   
                 domain (CTD) downstream of 
               
               
                   
                   
                 the NTD and CTD junction 
               
               
                   
                   
                 of the N protein 
               
               
                 3 
                 rVSV-N- 
                 71 AA region of CTD 
                 Comprises of two putative T-cell 
               
               
                   
                 CTL-2 
                   
                 epitopes 
               
               
                 4 
                 rVSV-N- 
                 38 AA region of NTD and 
                 Comprises of four putative T-cell 
               
               
                   
                 CTL-4 
                 CTD junction 
                 epitopes 
               
               
                 5 
                 rVSV-M 2-1   
                 Full-length wild type RSV- 
                 Shown to possess CTL epitopes 
               
               
                   
                   
                 M 2-1  protein 
               
               
                   
               
            
           
         
       
     
     When a human or non-human animal is challenged by a foreign organism/pathogen the challenged individual responds by launching an immune response which may be protective. This immune response is characterized by the coordinated interaction of the innate and acquired immune response systems. 
     The innate immune response forms the first line of defense against a foreign organism/pathogen. An innate immune response can be triggered within minutes of infection in an antigen-independent, but pathogen-dependent, manner. The innate, and indeed the adaptive, immune system can be triggered by the recognition of pathogen associated molecular patterns unique to microorganisms by pattern recognition receptors present on most host cells. Once triggered the innate system generates an inflammatory response that activates the cellular and humoral adaptive immune response systems. 
     The adaptive immune response becomes effective over days or weeks and provides the antigen specific responses needed to control and usually eliminate the foreign organism/pathogen. The adaptive response is mediated by T cells (cell mediated immunity) and B cells (antibody mediated or humoral immunity) that have developed specificity for the pathogen. Once activated these cells have a long lasting memory for the same pathogen. 
     The ability of an individual to generate immunity to foreign organisms/pathogens, thereby preventing or at least reducing the chance of infection by the foreign organism/pathogen, is a powerful tool in disease control and is the principle behind vaccination. 
     Vaccines function by preparing the immune system to mount a response to a pathogen. Typically, a vaccine comprises an antigen, which is a foreign organism/pathogen or a toxin produced by an organism/pathogen, or a portion thereof, that is introduced into the body of a subject to be vaccinated in a non-toxic, and/or non-pathogenic form. The antigen in the vaccine causes the subject&#39;s immune system to be “primed” or “sensitized” to the organism/pathogen from which the antigen is derived. Subsequent exposure of the immune system of the subject to the organism/pathogen or toxin results in a rapid and robust specific immune response, that controls or destroys the organism/pathogen or toxin before it can multiply and infect or damage enough cells in the host organism to cause disease symptoms. 
     Compositions 
     Disclosed herein are multiple rVSVs expressing one of the four different antigenic proteins (in natural or modified conformation) of RSV, which have been shown to be efficacious in a cotton rat animal model, with or without combining with an adjuvant expressing rVSV (rVSV-Hsp70). It has been demonstrated that when delivered intranasally, rVSVs expressing RSV proteins induce protective immunity in vaccinated cotton rats against wildtype RSV challenge. 
     Specifically, disclosed herein are compositions comprising a recombinant viral vector and one or more respiratory syncytial virus (RSV) proteins. The recombinant viral vector can be selected from recombinant viral vectors known to those of skill in the art. Non-limiting examples of vectors that can be used include viral-based vectors, such as those described in Lundstrom et al. ( Vaccines  2016, 4, 39), hereby incorporated by reference in its entirety for its teaching concerning viral vectors (e.g., retrovirus, adenovirus, adeno-associated virus, lentivirus, HMPV, PIV). Examples of rVSV that can be used include, but are not limited to the expression of G and F in one vector, G and N sequences or an expression of an RSV gene and HSP as adjuvant. HSP can be human or other. 
     As mentioned above and in Example 1, there are four categories of RSV proteins which can be used in the compositions disclosed herein. It is noted that RSV can be from any source, such as human, bovine, etc. The RSV proteins include the G protein, the F protein, the M2-1 protein, and the N protein. Further, the G protein is present in two forms, the membrane bound (mG) and secretory (sG) forms. Either form can be used with the compositions and methods disclosed herein. These proteins can be used alone in the composition, or can be presented together to increase the antigenic response. For example, the G protein can be coupled with N, M2-1, or F proteins. The mG protein can be coupled with N, M2-1, or F proteins. Any of these proteins can be combined in any possible permutation for use in an immunogenic composition or vaccine. The RSV proteins used in the compositions and vaccines disclosed herein can be full length, or can be functional immunogenic fragments that retain their immunogenicity when administered to a subject. One of skill in the art will readily understand how to obtain immunogenic fragments of an RSV protein. 
     Furthermore, the proteins disclosed herein can be codon optimized. For example, the codon optimization of G and pre-fusion conformation stabilized F leads to higher and more stable expression of these proteins. Sequences are listed in the sequences listing. “Codon optimization” is defined as modifying a nucleic acid sequence for enhanced expression in the cells of the vertebrate of interest, e.g. human, by replacing at least one, more than one, or a significant number, of codons of the native sequence with codons that are more frequently or most frequently used in the genes of that vertebrate. Various species exhibit particular bias for certain codons of a particular amino acid. 
     The composition disclosed herein can also comprise one or more adjuvants. As used herein, “adjuvant” is understood as an aid or contributor to increase the efficacy or potency of a vaccine or in the prevention, amelioration, or cure of disease by increasing the efficacy or potency of a therapeutic agent as compared to a vaccine or agent administered without the adjuvant. An increase in the efficacy or potency can include a decrease in the amount of vaccine or agent to be administered, a decrease in the frequency and/or number of doses to be administered, or a more rapid or robust response to the agent or vaccine (i.e., higher antibody titer). The adjuvant can be HSP70 (see  FIG. 4 ), but may also include alumn, detoxified monophosphoryl lipid A (MPLA), detoxified saponin derivative QS-21 or other pattern recognition receptor agonists including NLP and TLR agonists. Other variants of HSP70 will have a similar effect, whether they are from a different species or mutated as long as the binding domain is intact. 
     Described herein are vaccines comprising a composition of this invention in a carrier wherein the vaccine is protective against RSV infection. The term “immunogenic carrier” as used herein can refer to a first polypeptide or fragment, variant, or derivative thereof which enhances the immunogenicity of a second polypeptide or fragment, variant, or derivative thereof. An “immunogenic carrier” can be fused, to or conjugated/coupled to the desired polypeptide or fragment thereof. See, e.g., European Patent No. EP 0385610 B1, which is incorporated herein by reference in its entirety for its teaching of fusing, conjugating or coupling a polypeptide to a carrier. An example of an “immunogenic carrier” is PLGA. 
     The vaccine composition of the present invention may also be co-administered with antigens from other pathogens as a multivalent vaccine. 
     Methods of Use and Administration 
     Also disclosed herein are methods of using the immunogenic compositions and vaccines disclosed herein. For example, disclosed are methods of eliciting an immune response against RSV in a subject, the method comprising administering to the subject a composition or vaccine as disclosed herein. The immune response can be protective against RSV, for example. 
     Also disclosed is a method of reducing symptoms or duration of RSV in a subject, the method comprising the steps of: (a) providing a composition of any of claims  1  to  15  or the vaccine of claim  16 ; and (b) administering said composition or vaccine to the subject, thereby reducing symptoms or duration of RSV. 
     Further disclosed is a method of stimulating an immune response in a subject, the method comprising: administering to said subject a composition or vaccine as disclosed herein. 
     The vaccines disclosed herein can be administered in a variety of ways, and at a variety of doses. For example, intranasal route, orally, intramuscular route, intradermal and subcutaneous injection as well as application by ocular, vaginal and anal route. 
     In one example, a single dose of the immunogenic composition or vaccine can be given, wherein the composition comprises about 1×10 5  or more particles (which also are referred to as particle units (pu)) of the composition, e.g., about 1×10 6  or more particles, about 1×10′ or more particles, about 1×10 8  or more particles, about 1×10 9  or more particles, or about 3×10 8  or more particles of the composition. Alternatively, or in addition, a single dose of the composition comprises about 3×10 14  particles or less of the immunogenic composition, e.g., about 1×10 13  particles or less, about 1×10 12  particles or less, about 3×10 11  particles or less, about 1×10 11  particles or less, about 1×10 10  particles or less, or about 1×10 9  particles or less of the immunogenic composition. Thus, a single dose of immunogenic composition can comprise a quantity of particles of the immunogenic composition in a range defined by any two of the aforementioned values. For example, a single dose of immunogenic composition can comprise 1×10 5 -1×10 14  particles, 1×10 7 -1×10 12  particles, 1×10 8 -1×10 11  particles, 3×10 8 -3×10″ particles, 1×10 9 -1×10 12  particles, 1×10 9 -1×10 11  particles, 1×10 9 -1×10 10  particles, or 1×10 10 -1×10 12  particles, of the immunogenic composition. In other words, a single dose of immunogenic composition can comprise, for example, about 1×10 6  pu, 2×10 6  pu, 4×10 6  pu, 1×10 7  pu, 2×10 7  pu, 4×10 7  pu, 1×10 8  pu, 2×10 8  pu, 3×10 8  pu, 4×10 8  pu, 1×10 9  pu, 2×10 9  pu, 3×10 9  pu, 4×10 9  pu, 1×10 10  pu, 2×10 10  pu, 3×10 10  pu, 4×10 10  pu, 1×10 11  pu, 2×10 11  pu, 3×10 11  pu, 4×10 11  pu, 1×10 12  pu, 2×10 12  pu, 3×10 12  pu, or 4×10 12  pu of the adenoviral vector. 
     The vaccine can be given in single doses, or two doses which are separated. For example, when two doses are given, they can be given 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more days apart. The vaccine can be administered in a variety of ways known to those of skill in the art, such as intranasally. 
     EXAMPLES 
     Example 1: 10 7  Pfu/Dose/Animal of the rVSVs Expressing Wild Type G and F Proteins Induced Protective Immunity in Cotton Rats 
     Since 10 5  TCID 50 /dose of the RSV induced protective immunity in cotton rats (n=4 per group), therefore, for relative comparison of rVSVs with the RSV immune efficacy of the rVSV-G and rVSV-F recombinants, 10 5  pfu (plaque forming unit)/dose as the starting dose and also immunized with higher/10 fold incremental doses (10 6  pfu/animal or 10 7  pfu/animal) were evaluated. Cotton rats were immunized with either individual rVSV-G or rVSV-F recombinant or in combination (rVSV-G+F). The hypothesis was that rVSV induced protective effect is dose dependent and further, enhanced effect is possible by combining both G and F expressing rVSVs. Immunized animals were challenged with wild type RSV strain A2 (dose: 10 5  TCID 50 ) four weeks after vaccination and euthanized the animals four days after challenge. Clearance of the challenge virus was evaluated (by titrating the amount of virus using a cell culture cytopathic effect based assay) from the lower and upper respiratory tract (LRT and URT) represented by homogenates of the lungs and nasal passage respectively (collected on the day of euthanization) and virus neutralizing (VN) antibody levels (by cell culture based virus neutralization test) in the serum sample collected on the day of challenge. These studies demonstrated that non-invasive mucosal delivery of the rVSV-G or F by intranasal route was more effective than parental (by subcutaneous) route of administration. Therefore, for all subsequent studies, intranasal immunization method was employed. Further, it was also shown that 10 5  pfu/animal of either rVSV-G or rVSV-F was effective in clearance of challenge virus from the LRT but not URT along with lower VN antibody levels. Therefore, the objective of this study was to extend the protection to URT and enhance the VN antibody levels by employing higher dose and combined vaccination strategy. 
     The results indicated that, higher (each rVSV at 10 7  pfu/dose/cotton rat[CR]) and combined (rVSV-G+F) immunization strategy was effective in inducing protective immunity which could clear the challenge RSV from both LRT and URT ( FIGS. 2 a   &amp; b ) along with higher levels of VN antibody levels ( FIG. 2 c   ). 
     These results and the comparison of VSV expressing either G or F with immunization results through immunization with purified G and post-fusion F protein (Table 4) demonstrate that VSV vectors deliver a better immune response. 
     Example 2: Prime-Boost Immunization Regimen of rVSVs Expressing Wild Type G and F Proteins Induced Protective Immunity in Cotton Rats Along with Enhanced VN Titers 
     Though 10 7  pfu dose of rVSV-G and rVSV-F combination was adequate to protect the immunized cotton rats from the challenge virus, virus neutralization (VN) antibody titers were still lower than RSV-A2 immunized animals (which showed higher VN titer titers, ≥2 8 ). Therefore, to enhance the VN titers in rVSV immunized groups, it was hypothesized that by following prime-boost regimen of immunization strategy, VN titers can be significantly enhanced with high (10 7  pfu) and possibly with low dose (10 5  pfu) immunization as well. Therefore, cotton rats were immunized with either high dose or low dose of rVSVs, individually or in combination, and the booster dose was administered three weeks after primary immunization and the immunized cotton rats were challenged three weeks after booster immunization. 
     The results indicated that, at low dose immunization, neither individual nor combined rVSVs induced protective immunity in URT, and VN titers were also not considerably improved upon booster immunization. Whereas, in higher dose immunization groups, in all three groups VN antibodies were enhanced after booster immunization ( FIG. 3 c   ) along with complete protection of URT in rVSV-G and rVSV-G+F immunized groups ( FIGS. 3 a   &amp; b ). Prime-boost regimen was effective in enhancing the VN titers by up to 40% after booster immunization. Thus, it was evident from this study that, prime-boost immunization enhanced protective immunity in the immunized animals (and possibly indicating an extended longevity [i. e., memory immune response] of the protection). 
     Immunization can also be improved through the use of a VSV expressing HSP70 which functions as an adjuvant ( FIG. 4 ). 
     Example 3: Coupling of an Adjuvant Expressing rVSV Along with Prime-Boost Immunization Regimen of rVSVs Expressing Wild Type G and F Proteins Induced Enhanced Protective Immunity in Cotton Rats 
     Though prime-boost immunization with rVSV-G+F enhanced the VN titers (titer: ˜2 6 ), however, the VN titers in RSV-A2 immunized animals were significantly higher (titer: &gt;2 8 ). Therefore, with an objective to further enhancing the protective immunity in the rVSV-G+F immunized animals and to explore a possibility of extending the longevity of the protection, the vaccine rVSV candidates were combined with Hsp70 expressing rVSV (rVSV-Hsp-70). It has been demonstrated that rVSV-Hsp70 enhanced adjuvanticity of the vaccine antigen co-expressing rVSV (Ma, et al., 2014) resulting in enhanced mucosal immunity. Further the safe dose of rVSV-Hsp70 (i. e., ≤10 7  pfu/dose/CR) has been shown in cotton rats. Therefore, in the present study, with an objective to identify the appropriate dose of rVSV-Hsp70 along with rVSV-G+F, cotton rats were immunized (following prime-boost regimen) with either high dose or low dose combination of rVSV-G+F and combined with one of the three doses (10 5 , 10 6 , or 10 7  pfu/dose/CR) of the rVSV-Hsp70. 
     The results indicated that, 10 5  pfu dose of the rVSV-Hsp70 was an appropriate dose along with high dose of the rVSV-G+F as there was complete protection of both LRT and URT ( FIGS. 4 a   &amp; b ) along with enhanced VN titers by 33% ( FIG. 4 c   ). 
     It is clearly evident from the above studies that, prime-boost immunization of the 10 7  pfu dose of each of rVSV-G and rVSV-F combination induced enhanced protective immunity in the cotton rat model. Further, efficacy of the combination (and possibly longevity of the protection) can be further enhanced by inclusion of the adjuvant expressing rVSV-Hsp70. 
     Example 4: Codon-Optimized or Membrane-Bound Codon Optimized RSV G Protein Expressing rVSVs (rVSV-cG or rVSV-mG) were More Effective than Wild-Type G (rVSV-G) in Inducing Protective Immunity in the URT Along with Enhanced VN Titers 
     In order to identify an effective G protein candidate, several modifications were made to the G protein to enhance its immunogenicity as explained in table 1 (S. No. 2-9) and expressed the indicated G variant in the VSV vector and tested the efficacy in the cotton rats. Cotton rats were immunized with each of the seven recovered rVSV G variants, following the previously established strategy for the rVSV-G+F immunization studies (i. e., high dose [10 7  pfu/dose/CR] and prime-boost immunization). 
     The results clearly indicated that among all the tested G variants, two recombinants (rVSV-cG and rVSV-mG) were successful in inducing protective immunity in the in the URT ( FIGS. 5 a   &amp; b ) as well as enhanced VN titers compared to rVSV-G ( FIG. 5 c   ). These results demonstrated that, either expressing the codon-optimized G protein (which produces higher levels of both membrane bound as well as secretory forms) at higher level endogenously or expressing it exclusively in the membrane bound form (by excluding the ‘decoy’ effect of the secretory G), it is possible to induce protective immunity by RSV G protein alone. Further, single dose immunization with 10 5 , 10 6 , or 10 7  dose of rVSV-cG or rVSV-mG was tested for effectiveness in eliciting protective immunity. The results demonstrated that higher dose (10 7  pfu) of the either recombinant was effective in either completely protecting the URT (rVSV-cG) or reducing the challenge virus titer (rVSV-mG) ( FIG. 6 b   ). However, the VN titers in all the groups were low and comparable ( FIG. 6 c   ). These results demonstrated that, even though modified G recombinants (cG and mG) alone were effective in protecting both LRT and URT, however, to induce enhanced VN antibodies, prime-boost immunization regimen is essential. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Immunization with G and F protein. G and post-fusion F protein 
               
               
                 were expressed eucaryotically in 293F cells. Cotton rats were immunized 
               
               
                 with 5 ug of purified protein in 200 ul alumn subcutaneously. Four weeks 
               
               
                 later, blood was drawn to determine neutralizing antibody titers and 
               
               
                 animals were challenged with 10 5  TCID 50  RSV. 
               
               
                 Four days later, virus titers were determined from lung and nasal tissue. 
               
               
                 Post-fusion F is currently tested in clinical trials. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Neutralizing 
               
               
                   
                 Nose 
                 Lung 
                 antibody 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Naïve animals 
                 3.8 ± 0.2 
                 3.4 ± 0.3 
                 2 0   
               
               
                   
                 Immunized with G 
                 3.9 ± 0.4 
                 3.9 ± 0.4 
                 2 0   
               
               
                   
                 protein 
               
               
                   
                 Immunized with 
                 0 
                 0 
                 2 4.5   
               
               
                   
                 post-F protein 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                 SEQUENCES 
               
               
                   
               
             
            
               
                 Sequences of RSV genes expressed in the VSV expression system 
               
               
                 SEQ ID NO: 1: RSV-G (Size: 897 nts) 
               
               
                 ATGTCCAAAAACAAGGACCAACGCACCGCTAAGACATTAGAAAGGACCTGG 
               
               
                 GACACTCTCAATCATTTATTATTCATATCATCGTGCTTATATAAGTTAAATCTTAAAT 
               
               
                 CTGTAGCACAAATCACATTATCCATTCTGGCAATGATAATCTCAACTTCACTTATAA 
               
               
                 TTGCAGCCATCATATTCATAGCCTCGGCAAACCACAAAGTCACACCAACAACTGCA 
               
               
                 ATCATACAAGATGCAACAAGCCAGATCAAGAACACAACCCCAACATACCTCACCCA 
               
               
                 GAATCCTCAGCTTGGAATCAGTCCCTCTAATCCGTCTGAAATTACATCACAAATCAC 
               
               
                 CACCATACTAGCTTCAACAACACCAGGAGTCAAGTCAACCCTGCAATCCACAACAG 
               
               
                 TCAAGACCAAAAACACAACAACAACTCAAACACAACCCAGCAAGCCCACCACAAA 
               
               
                 ACAACGCCAAAACAAACCACCAAGCAAACCCAATAATGATTTTCACTTTGAAGTGT 
               
               
                 TCAACTTTGTACCCTGCAGCATATGCAGCAACAATCCAACCTGCTGGGCTATCTGCA 
               
               
                 AAAGAATACCAAACAAAAAACCAGGAAAGAAAACCACTACCAAGCCCACAAAAAA 
               
               
                 ACCAACCCTCAAGACAACCAAAAAAGATCCCAAACCTCAAACCACTAAATCAAAGG 
               
               
                 AAGTACCCACCACCAAGCCCACAGAAGAGCCAACCATCAACACCACCAAAACAAAC 
               
               
                 ATCATAACTACACTACTCACCTCCAACACCACAGGAAATCCAGAACTCACAAGTCA 
               
               
                 AATGGAAACCTTCCACTCAACTTCCTCCGAAGGCAATCCAAGCCCTTCTCAAGTCTC 
               
               
                 TACAACATCCGAGTACCCATCACAACCTTCATCTCCACCCAACACACCACGCCAGTA 
               
               
                 G 
               
               
                   
               
               
                 SEQ ID NO: 2: RSV-cG Icodon optimized G] (size :897 nts) 
               
               
                 ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACCCTGGAGCGGACCTGG 
               
               
                 GACACCCTGAACCACCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAG 
               
               
                 AGCGTGGCCCAGATCACCCTGAGCATCCTGGCCATGATCATCAGCACCAGCCTGATC 
               
               
                 ATCGCCGCCATCATCTTCATCGCCAGCGCCAACCACAAGGTGACCCCCACCACCGCC 
               
               
                 ATCATCCAGGACGCCACCAGCCAGATCAAGAACACCACCCCCACCTACCTGACCCA 
               
               
                 GAACCCCCAGCTGGGCATCAGCCCCAGCAACCCCAGCGAGATCACCAGCCAGATCA 
               
               
                 CCACCATCCTGGCCAGCACCACCCCCGGCGTGAAGAGCACCCTGCAGAGCACCACC 
               
               
                 GTGAAGACCAAGAACACCACCACCACCCAGACCCAGCCCAGCAAGCCCACCACCAA 
               
               
                 GCAGCGGCAGAACAAGCCTCCCAGCAAGCCCAACAACGACTTCCACTTCGAGGTGT 
               
               
                 TCAACTTCGTGCCCTGCAGCATCTGCAGCAACAACCCCACCTGCTGGGCCATCTGCA 
               
               
                 AGCGGATTCCCAACAAGAAGCCCGGCAAGAAGACCACCACCAAGCCCACCAAGAA 
               
               
                 GCCCACCCTGAAGACCACCAAGAAGGACCCCAAGCCCCAGACCACCAAGAGCAAG 
               
               
                 GAGGTGCCCACCACCAAGCCCACCGAGGAGCCCACCATCAACACCACCAAGACCAA 
               
               
                 CATCATCACCACCCTGCTGACCAGCAACACCACCGGCAACCCCGAGCTGACCAGCC 
               
               
                 AGATGGAGACCTTCCACAGCACCAGCAGCGAGGGCAACCCCAGCCCCAGCCAGGTG 
               
               
                 AGCACCACCAGCGAGTACCCCAGCCAGCCCAGCAGCCCTCCCAACACCCCTCGGCA 
               
               
                 GTAG 
               
               
                   
               
               
                 SEQ ID NO: 3: RSV-cmG [codon optimized membrane bound G] 
               
               
                 (size: 897 nts) 
               
               
                 ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACCCTGGAGCGGACCTGG 
               
               
                 GACACCCTGAACCACCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAG 
               
               
                 AGCGTGGCCCAGATCACCCTGAGCATCCTGGCCATTATCATCAGCACCAGCCTGATC 
               
               
                 ATCGCCGCCATCATCTTCATCGCCAGCGCCAACCACAAGGTGACCCCCACCACCGCC 
               
               
                 ATCATCCAGGACGCCACCAGCCAGATCAAGAACACCACCCCCACCTACCTGACCCA 
               
               
                 GAACCCCCAGCTGGGCATCAGCCCCAGCAACCCCAGCGAGATCACCAGCCAGATCA 
               
               
                 CCACCATCCTGGCCAGCACCACCCCCGGCGTGAAGAGCACCCTGCAGAGCACCACC 
               
               
                 GTGAAGACCAAGAACACCACCACCACCCAGACCCAGCCCAGCAAGCCCACCACCAA 
               
               
                 GCAGCGGCAGAACAAGCCTCCCAGCAAGCCCAACAACGACTTCCACTTCGAGGTGT 
               
               
                 TCAACTTCGTGCCCTGCAGCATCTGCAGCAACAACCCCACCTGCTGGGCCATCTGCA 
               
               
                 AGCGGATTCCCAACAAGAAGCCCGGCAAGAAGACCACCACCAAGCCCACCAAGAA 
               
               
                 GCCCACCCTGAAGACCACCAAGAAGGACCCCAAGCCCCAGACCACCAAGAGCAAG 
               
               
                 GAGGTGCCCACCACCAAGCCCACCGAGGAGCCCACCATCAACACCACCAAGACCAA 
               
               
                 CATCATCACCACCCTGCTGACCAGCAACACCACCGGCAACCCCGAGCTGACCAGCC 
               
               
                 AGATGGAGACCTTCCACAGCACCAGCAGCGAGGGCAACCCCAGCCCCAGCCAGGTG 
               
               
                 AGCACCACCAGCGAGTACCCCAGCCAGCCCAGCAGCCCTCCCAACACCCCTCGGCA 
               
               
                 GTAG 
               
               
                   
               
               
                 SEQ ID NO: 4: RSV-G(C1865) (Size: 897 nts) 
               
               
                 ATGAGCAAGAACAAGGACCAGCGGACCGCCAAGACCCTGGAGCGGACCTGG 
               
               
                 GACACCCTGAACCACCTGCTGTTCATCAGCAGCTGCCTGTACAAGCTGAACCTGAAG 
               
               
                 AGCGTGGCCCAGATCACCCTGAGCATCCTGGCCATGATCATCAGCACCAGCCTGATC 
               
               
                 ATCGCCGCCATCATCTTCATCGCCAGCGCCAACCACAAGGTGACCCCCACCACCGCC 
               
               
                 ATCATCCAGGACGCCACCAGCCAGATCAAGAACACCACCCCCACCTACCTGACCCA 
               
               
                 GAACCCCCAGCTGGGCATCAGCCCCAGCAACCCCAGCGAGATCACCAGCCAGATCA 
               
               
                 CCACCATCCTGGCCAGCACCACCCCCGGCGTGAAGAGCACCCTGCAGAGCACCACC 
               
               
                 GTGAAGACCAAGAACACCACCACCACCCAGACCCAGCCCAGCAAGCCCACCACCAA 
               
               
                 GCAGCGGCAGAACAAGCCTCCCAGCAAGCCCAACAACGACTTCCACTTCGAGGTGT 
               
               
                 TCAACTTCGTGCCCTGCAGCATCTGCAGCAACAACCCCACCTGCTGGGCCATCTCCA 
               
               
                 AGCGGATTCCCAACAAGAAGCCCGGCAAGAAGACCACCACCAAGCCCACCAAGAA 
               
               
                 GCCCACCCTGAAGACCACCAAGAAGGACCCCAAGCCCCAGACCACCAAGAGCAAG 
               
               
                 GAGGTGCCCACCACCAAGCCCACCGAGGAGCCCACCATCAACACCACCAAGACCAA 
               
               
                 CATCATCACCACCCTGCTGACCAGCAACACCACCGGCAACCCCGAGCTGACCAGCC 
               
               
                 AGATGGAGACCTTCCACAGCACCAGCAGCGAGGGCAACCCCAGCCCCAGCCAGGTG 
               
               
                 AGCACCACCAGCGAGTACCCCAGCCAGCCCAGCAGCCCTCCCAACACCCCTCGGCA 
               
               
                 GTAG 
               
               
                   
               
               
                 SEQ ID NO: 5: RSV-Sec G (756 nts) 
               
               
                 ATGATCATCAGCACCAGCCTGATCATCGCCGCCATCATCTTCATCGCCAGCGC 
               
               
                 CAACCACAAGGTGACCCCCACCACCGCCATCATCCAGGACGCCACCAGCCAGATCA 
               
               
                 AGAACACCACCCCCACCTACCTGACCCAGAACCCCCAGCTGGGCATCAGCCCCAGC 
               
               
                 AACCCCAGCGAGATCACCAGCCAGATCACCACCATCCTGGCCAGCACCACCCCCGG 
               
               
                 CGTGAAGAGCACCCTGCAGAGCACCACCGTGAAGACCAAGAACACCACCACCACCC 
               
               
                 AGACCCAGCCCAGCAAGCCCACCACCAAGCAGCGGCAGAACAAGCCTCCCAGCAA 
               
               
                 GCCCAACAACGACTTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAG 
               
               
                 CAACAACCCCACCTGCTGGGCCATCTGCAAGCGGATTCCCAACAAGAAGCCCGGCA 
               
               
                 AGAAGACCACCACCAAGCCCACCAAGAAGCCCACCCTGAAGACCACCAAGAAGGA 
               
               
                 CCCCAAGCCCCAGACCACCAAGAGCAAGGAGGTGCCCACCACCAAGCCCACCGAGG 
               
               
                 AGCCCACCATCAACACCACCAAGACCAACATCATCACCACCCTGCTGACCAGCAAC 
               
               
                 ACCACCGGCAACCCCGAGCTGACCAGCCAGATGGAGACCTTCCACAGCACCAGCAG 
               
               
                 CGAGGGCAACCCCAGCCCCAGCCAGGTGAGCACCACCAGCGAGTACCCCAGCCAGC 
               
               
                 CCAGCAGCCCTCCCAACACCCCTCGGCAGTAG 
               
               
                   
               
               
                 SEQ ID NO: 6: RSV-GΔNg (897nts) 
               
               
                 ATGTCTAAAAACAAGGATCAGCGAACCGCCAAAACCCTGGAGCGTACATGG 
               
               
                 GATACACTCAACCACCTTCTGTTCATATCTAGCTGCCTTTACAAACTTAATCTCAAAA 
               
               
                 GCGTCGCCCAGATTACCCTCTCAATACTGGCTATGATAATCTCCACCTCTTTGATAAT 
               
               
                 AGCCGCTATCATTTTCATAGCTTCTGCAAACCACAAAGTAACTCCAACCACAGCTAT 
               
               
                 AATACAAGATGCCACCTCTCAGATTAAAAATACCACACCCACATATCTTACTCAGAA 
               
               
                 TCCTCAATTGGGAATCAGCCCATCTAAgCCATCCGAGATTACTTCACAGATCACCAC 
               
               
                 AATACTCGCATCCACAACACCAGGGGTCAAATCCACCCTGCAATCAACTACCGTGA 
               
               
                 AAACTAAAAAgACCACTACAACACAGACTCAACCCAGCAAGCCTACAACAAAGCAA 
               
               
                 CGCCAGAATAAGCCACCTTCTAAGCCAAACAATGATTTCCATTTTGAGGTCTTTAAT 
               
               
                 TTCGTGCCTTGCTCTATATGTTCCAACAAgCCAACTTGCTGGGCCATTTGCAAACGCA 
               
               
                 TCCCAAATAAGAAACCCGGTAAGAAAACCACAACCAAGCCAACTAAAAAGCCAACT 
               
               
                 TTGAAGACTACCAAAAAGGACCCTAAGCCCCAGACAACTAAATCAAAAGAAGTCCC 
               
               
                 AACTACTAAGCCAACTGAGGAACCAACAATAAAgACTACAAAAACCAACATCATCA 
               
               
                 CAACCCTTCTTACTAGCAAgACTACTGGTAACCCCGAGCTGACAAGCCAGATGGAGA 
               
               
                 CATTCCACAGTACAAGCAGCGAAGGAAACCCAAGCCCTAGTCAAGTGTCCACTACC 
               
               
                 TCAGAATACCCCAGCCAGCCTTCCTCACCTCCTAACACACCCCGGCAATAG 
               
               
                   
               
               
                 SEQ ID NO: 7: RSV-mGΔNg (897nts) 
               
               
                 cagcaatctcgagATGTCTAAAAACAAGGATCAGCGAACCGCCAAAACCCTGGAGC 
               
               
                 GTACATGGGATACACTCAACCACCTTCTGTTCATATCTAGCTGCCTTTACAAACTTA 
               
               
                 ATCTCAAAAGCGTCGCCCAGATTACCCTCTCAATACTGGCT ATT ATAATCTCCACCTC 
               
               
                 TTTGATAATAGCCGCTATCATTTTCATAGCTTCTGCAAACCACAAAGTAACTCCAAC 
               
               
                 CACAGCTATAATACAAGATGCCACCTCTCAGATTAAAAATACCACACCCACATATCT 
               
               
                 TACTCAGAATCCTCAATTGGGAATCAGCCCATCTAAgCCATCCGAGATTACTTCACA 
               
               
                 GATCACCACAATACTCGCATCCACAACACCAGGGGTCAAATCCACCCTGCAATCAA 
               
               
                 CTACCGTGAAAACTAAAAAgACCACTACAACACAGACTCAACCCAGCAAGCCTACA 
               
               
                 ACAAAGCAACGCCAGAATAAGCCACCTTCTAAGCCAAACAATGATTTCCATTTTGA 
               
               
                 GGTCTTTAATTTCGTGCCTTGCTCTATATGTTCCAACAAgCCAACTTGCTGGGCCATT 
               
               
                 TGCAAACGCATCCCAAATAAGAAACCCGGTAAGAAAACCACAACCAAGCCAACTAA 
               
               
                 AAAGCCAACTTTGAAGACTACCAAAAAGGACCCTAAGCCCCAGACAACTAAATCAA 
               
               
                 AAGAAGTCCCAACTACTAAGCCAACTGAGGAACCAACAATAAAgACTACAAAAACC 
               
               
                 AACATCATCACAACCCTTCTTACTAGCAAgACTACTGGTAACCCCGAGCTGACAAGC 
               
               
                 CAGATGGAGACATTCCACAGTACAAGCAGCGAAGGAAACCCAAGCCCTAGTCAAGT 
               
               
                 GTCCACTACCTCAGAATACCCCAGCCAGCCTTCCTCACCTCCTAACACACCCCGGCA 
               
               
                 ATAGcccgggttcat 
               
               
                   
               
               
                 SEQ ID NO: 8: RSV-G (aa 163-190) (84 nts) 
               
               
                 TTCCACTTCGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAACCC 
               
               
                 CACCTGCTGGGCCATCTGCAAGCGGATTCCC 
               
               
                   
               
               
                 SEQ ID NO: 9: RSV-G (aa 130-230) (303 nts) 
               
               
                 ACCGTGAAGACCAAGAACACCACCACCACCCAGACCCAGCCCAGCAAGCCC 
               
               
                 ACCACCAAGCAGCGGCAGAACAAGCCTCCCAGCAAGCCCAACAACGACTTCCACTT 
               
               
                 CGAGGTGTTCAACTTCGTGCCCTGCAGCATCTGCAGCAACAACCCCACCTGCTGGGC 
               
               
                 CATCTGCAAGCGGATTCCCAACAAGAAGCCCGGCAAGAAGACCACCACCAAGCCCA 
               
               
                 CCAAGAAGCCCACCCTGAAGACCACCAAGAAGGACCCCAAGCCCCAGACCACCAA 
               
               
                 GAGCAAGGAGGTGCCCACCACCAAGCCC 
               
               
                   
               
               
                 SEQ ID NO: 10: RSV-F (size: 1725 nts) 
               
               
                 ATGGAGTTGCTAATCCTCAAAGCAAATGCAATTACCACAATCCTCACTGCAG 
               
               
                 TCACATTTTGTTTTGCTTCTGGTCAAAACATCACTGAAGAATTTTATCAATCAACATG 
               
               
                 CAGTGCAGTTAGCAAAGGCTATCTTAGTGCTCTGAGAACTGGTTGGTATACCAGTGT 
               
               
                 TATAACTATAGAATTAAGTAATATCAAGAAAAATAAGTGTAATGGAACAGATGCTA 
               
               
                 AGGTAAAATTGATAAAACAAGAATTAGATAAATATAAAAATGCTGTAACAGAATTG 
               
               
                 CAGTTGCTCATGCAAAGCACACAAGCAACAAACAATCGAGCCAGAAGAGAACTACC 
               
               
                 AAGGTTTATGAATTATACACTCAACAATGCCAAAAAAACCAATGTAACATTAAGCA 
               
               
                 AGAAAAGGAAAAGAAGATTTCTTGGTTTTTTGTTAGGTGTTGGATCTGCAATCGCCA 
               
               
                 GTGGCGTTGCTGTATCTAAGGTCCTGCACCTAGAAGGGGAAGTGAACAAGATCAAA 
               
               
                 AGTGCTCTACTATCCACAAACAAGGCTGTAGTCAGCTTATCAAATGGAGTTAGTGTT 
               
               
                 TTAACCAGCAAAGTGTTAGACCTCAAAAACTATATAGATAAACAATTGTTACCTATT 
               
               
                 GTGAACAAGCAAAGCTGCAGCATATCAAATATAGAAACTGTGATAGAGTTCCAACA 
               
               
                 AAAGAACAACAGACTACTAGAGATTACCAGGGAATTTAGTGTTAATGCAGGCGTAA 
               
               
                 CTACACCTGTAAGCACTTACATGTTAACTAATAGTGAATTATTGTCATTAATCAATG 
               
               
                 ATATGCCTATAACAAATGATCAGAAAAAGTTAATGTCCAACAATGTTCAAATAGTTA 
               
               
                 GACAGCAAAGTTACTCTATCATGTCCATAATAAAAGAGGAAGTCTTAGCATATGTA 
               
               
                 GTACAATTACCACTATATGGTGTTATAGATACACCCTGTTGGAAACTACACACATCC 
               
               
                 CCTCTATGTACAACCAACACAAAAGAAGGGTCCAACATCTGTTTAACAAGAACTGA 
               
               
                 CAGAGGATGGTACTGTGACAATGCAGGATCAGTATCTTTCTTCCCACAAGCTGAAAC 
               
               
                 ATGTAAAGTTCAATCAAATCGAGTATTTTGTGACACAATGAACAGTTTAACATTACC 
               
               
                 AAGTGAAGTAAATCTCTGCAATGTTGACATATTCAACCCCAAATATGATTGTAAAAT 
               
               
                 TATGACTTCAAAAACAGATGTAAGCAGCTCCGTTATCACATCTCTAGGAGCCATTGT 
               
               
                 GTCATGCTATGGCAAAACTAAATGTACAGCATCCAATAAAAATCGTGGAATCATAA 
               
               
                 AGACATTTTCTAACGGGTGCGATTATGTATCAAATAAAGGGGTGGACACTGTGTCTG 
               
               
                 TAGGTAACACATTATATTATGTAAATAAGCAAGAAGGTAAAAGTCTCTATGTAAAA 
               
               
                 GGTGAACCAATAATAAATTTCTATGACCCATTAGTATTCCCCTCTGATGAATTTGAT 
               
               
                 GCATCAATATCTCAAGTCAACGAGAAGATTAACCAGAGCCTAGCATTTATTCGTAAA 
               
               
                 TCCGATGAATTATTACATAATGTAAATGCTGGTAAATCCACCACAAATATCATGATA 
               
               
                 ACTACTATAATTATAGTGATTATAGTAATATTGTTATCATTAATTGCTGTTGGACTGC 
               
               
                 TCTTATACTGTAAGGCCAGAAGCACACCAGTCACACTAAGCAAAGATCAACTGAGT 
               
               
                 GGTATAAATAATATTGCATTTAGTAACTAA 
               
               
                   
               
               
                 SEQ ID NO: 11: RSV-Pre-F-Foldon (1941 nts) 
               
               
                 ATGGAGCTGCTCATCCTGAAGGCCAACGCCATCACCACCATCCTCACCGCCG 
               
               
                 TGACCTTCTGCTTCGCCAGCGGCCAGAATATCACAGAGGAATTTTATCAGTCTACTT 
               
               
                 GTAGTGCCGTCAGTAAAGGATATCTGAGCGCTCTCAGAACAGGATGGTACACTAGT 
               
               
                 GTTATTACAATAGAATTGTCAAATATCAAGAAAAATAAGTGCAACGGTACTGACGC 
               
               
                 TAAGGTTAAGCTCATCAAACAGGAACTTGATAAATATAAGAACGCAGTTACAGAAC 
               
               
                 TTCAGCTTCTTATGCAGTCCACACAAGCCACCAATAATAAAGCTAAAAAAGAACTCC 
               
               
                 CACGGTTCATGAACTACACACTGAACAATGCAAAAAAAACCAACGTAACCCTTAGC 
               
               
                 AAGAAAAAGAAAAAAAAGTTCCTTGGCTTCCTCCTCGGAGTAGGCAGCGCTATTGC 
               
               
                 AAGTGGGGTAGCCGTGTGTAAGGTTTTGCATCTCGAAGGAGAAGTGAATAAAATAA 
               
               
                 AGAGCGCCTTGCTGTCCACTAATAAGGCCGTAGTCAGCCTTAGCAATGGCGTATCCG 
               
               
                 TTCTGACCTTTAAAGTACTGGATTTGAAGAACTACATCGATAAACAGCTTCTCCCCA 
               
               
                 TTTTGAATAAGCAATCATGTTCTATCAGTAACATAGAAACCGTCATCGAATTCCAAC 
               
               
                 AAAAAAACAATCGGCTTTTGGAAATAACTCGTGAATTTTCTGTAAACGCAGGCGTG 
               
               
                 ACAACTCCCGTATCAACCTACATGTTGACCAATAGCGAACTGCTGTCACTCATTAAC 
               
               
                 GACATGCCAATCACTAACGACCAGAAAAAACTTATGAGCAATAATGTACAGATTGT 
               
               
                 AAGACAGCAAAGTTACAGCATAATGTGCATTATTAAGGAAGAAGTTTTGGCATACG 
               
               
                 TTGTCCAACTCCCCCTTTATGGGGTCATTGATACCCCCTGCTGGAAGCTGCATACTA 
               
               
                 GCCCATTGTGTACTACCAACACCAAAGAGGGTAGTAACATATGCCTCACCAGAACT 
               
               
                 GACCGAGGCTGGTACTGTGATAATGCTGGAAGTGTCAGTTTCTTTCCTCAAGCAGAG 
               
               
                 ACCTGCAAAGTTCAGTCCAACCGCGTGTTCTGTGATACAATGAACTCCCTGACACTC 
               
               
                 CCTAGCGAAGTCAACCTTTGTAACGTCGATATATTTAATCCTAAATACGATTGTAAG 
               
               
                 ATCATGACTTCAAAAACTGACGTATCCTCTTCCGTTATTACTTCTTTGGGTGCCATAG 
               
               
                 TTAGTTGCTACGGCAAAACAAAATGCACCGCATCTAATAAAAACAGAGGAATTATT 
               
               
                 AAGACATTTTCAAATGGTTGCGACTACGTTAGTAATAAAGGTGTAGATACAGTAAGT 
               
               
                 GTTGGTAACACCCTCTATTACGTGAACAAACAGGAAGGGAAAAGCCTGTACGTGAA 
               
               
                 AGGGGAGCCCATAATCAACTTCTACGACCCCCTTGTATTTCCTAGTGATGAATTTGA 
               
               
                 CGCCTCCATCAGTCAAGTGAACGAAAAGATCAACCAAAGCCTTGCTTTCATCCGCAA 
               
               
                 ATCCGATGAGTTGCTCCACAATATTAAAGGCTCGGGATATATACCGGAGGCCCCGC 
               
               
                 GAGATGGTCAAGCTTATGTGCGCAAAGACGGTGAGTGGGTCTTGTTATCTACATTTT 
               
               
                 TGGGTAACACTAATAGTGGAGGTAGCACGACGACAATTACTAATAATAACTCGGGA 
               
               
                 ACTAACTCAAGCTCCACTACCTACACTGTCAAATCTGGTGATACATTGTGGGGCATA 
               
               
                 AGTCAAAGATATGGTATTTCAGTAGCCCAAATTCAATCGGCGAATAATTTAAAGAG 
               
               
                 CACAATAATTTACATAGGCCAGAAGCTCGTCCTGACAGGTTCCGCCTCGTCAACCAA 
               
               
                 TAGCGGAGGCAGCAACAACAGTGCTTCAACGACACCCACCACCTCGGTTACTCCTG 
               
               
                 CTAAGCCAACAAGTCAAACAACT 
               
               
                   
               
               
                 SEQ ID NO: 12: hCdn. RSV-Pre-F (1725 nts) 
               
               
                 ATGGAACTTCTTATATTGAAGGCAAACGCAATCACCACCATTTTGACTGCGGT 
               
               
                 TACATTCTGTTTCGCCTCAGGTCAAAATATTACAGAAGAATTCTACCAGAGCACATG 
               
               
                 CTCAGCGGTATCAAAGGGTTACTTGTCAGCCCTTAGGACCGGATGGTATACCTCTGT 
               
               
                 AATAACAATAGAACTTTCAAACATTAAAAAAAATAAGTGCAACGGGACCGATGCAA 
               
               
                 AAGTTAAACTGATCAAGCAAGAACTGGACAAGTATAAAAACGCAGTCACTGAACTT 
               
               
                 CAACTTCTTATGCAGTCCACGCAAGCCACTAATAATAAGGCTAAGAAAGAACTGCC 
               
               
                 AAGGTTTATGAACTATACCCTGAACAACGCGAAGAAGACTAATGTCACGTTGTCAA 
               
               
                 AAAAGAAAAAGAAAAAATTCCTGGGGTTCCTGCTCGGAGTAGGCAGTGCAATCGCG 
               
               
                 TCTGGAGTAGCCGTATGTAAAGTATTGCACCTTGAAGGAGAAGTAAACAAAATAAA 
               
               
                 GAGCGCTCTGCTCTCTACGAACAAAGCTGTTGTAAGTCTGAGCAATGGCGTCTCAGT 
               
               
                 CCTGACATTTAAAGTTCTTGATTTGAAAAATTATATTGACAAACAACTCCTCCCTATC 
               
               
                 CTCAACAAACAGTCTTGCTCTATTTCAAATATTGAGACAGTTATCGAATTTCAGCAA 
               
               
                 AAAAACAATAGGCTCCTTGAAATCACACGAGAATTTTCTGTAAACGCTGGAGTCAC 
               
               
                 AACACCAGTATCTACGTATATGCTCACCAATTCCGAACTTCTTTCATTGATAAATGA 
               
               
                 TATGCCCATAACAAACGACCAGAAAAAATTGATGTCCAATAATGTCCAAATCGTTC 
               
               
                 GCCAACAGAGCTATTCTATCATGTGTATAATAAAAGAGGAAGTTCTCGCTTACGTTG 
               
               
                 TCCAACTGCCGCTGTACGGGGTGATTGACACACCTTGCTGGAAACTTCATACTAGCC 
               
               
                 CTCTGTGCACGACTAACACCAAGGAAGGATCAAATATCTGCCTCACGCGAACTGAC 
               
               
                 AGGGGTTGGTACTGTGATAACGCTGGTTCCGTGTCATTTTTTCCTCAAGCTGAGACG 
               
               
                 TGTAAAGTACAGTCCAATCGAGTTTTCTGCGATACTATGAACTCACTCACCTTGCCG 
               
               
                 TCAGAGGTGAACCTCTGTAACGTAGATATATTTAACCCGAAATACGACTGTAAGATT 
               
               
                 ATGACTTCAAAGACCGATGTGTCAAGCTCCGTCATTACCTCCTTGGGAGCAATTGTT 
               
               
                 TCTTGCTATGGTAAGACGAAGTGCACTGCGAGCAACAAGAATCGCGGTATCATCAA 
               
               
                 GACGTTCTCCAACGGATGCGATTATGTAAGTAACAAGGGAGTTGACACGGTGAGTG 
               
               
                 TAGGGAACACGTTGTACTATGTAAACAAGCAGGAGGGGAAGTCCTTGTATGTCAAG 
               
               
                 GGCGAACCTATTATCAACTTCTACGACCCATTGGTGTTCCCTAGTGACGAGTTTGAT 
               
               
                 GCTAGTATTTCCCAGGTCAACGAGAAGATAAACCAAAGTTTGGCTTTCATTAGGAAG 
               
               
                 AGCGATGAGCTTCTCCACAATGTGAACGCCGGGAAGAGTACGACTAATATTATGAT 
               
               
                 CACAACCATCATAATCGTCATTATCGTTATTTTGCTCTCACTGATTGCAGTCGGACTT 
               
               
                 CTGCTGTACTGCAAAGCTCGCAGTACCCCAGTCACGCTTTCCAAGGACCAACTTTCA 
               
               
                 GGCATTAATAACATCGCATTTTCTAATTAA 
               
               
                   
               
               
                 SEQ ID NO: 13: hCdn. RSV-Post-F (1509 nts) 
               
               
                 ATGGAACTTTTGATACTGAAGGCGAACGCCATAACGACGATCCTGACAGCTG 
               
               
                 TAACTTTTTGCTTCGCGAGCGGTCAAAACATAACCGAGGAATTTTATCAGTCAACGT 
               
               
                 GCTCTGCTGTTAGCAAAGGATATCTCAGCGCACTCAGGACGGGCTGGTACACGTCA 
               
               
                 GTCATAACGATTGAGCTGTCTAATATCAAGAAGAACAAATGCAACGGAACGGACGC 
               
               
                 CAAAGTCAAGCTCATAAAACAAGAATTGGACAAGTACAAGAATGCTGTGACGGAGC 
               
               
                 TTCAGCTCTTGATGCAGTCCACCCAAGCGACGAATAATAGAGCGAGGAGAGAGCTC 
               
               
                 CCAAGATTTATGAACTATACACTGAACAATGCAAAGAAGACTAATGTGACCCTTAG 
               
               
                 CAAGAAAAGAAAAAGAAGAGCGATTGCAAGTGGAGTGGCTGTGTCAAAGGTCCTG 
               
               
                 CACCTTGAAGGTGAGGTGAACAAGATTAAATCCGCGCTGCTTTCTACGAACAAAGC 
               
               
                 TGTCGTTAGTTTGTCCAATGGCGTTTCAGTGCTCACTTCCAAGGTATTGGATTTGAAG 
               
               
                 AATTATATTGACAAACAGCTCCTTCCGATTGTTAATAAACAGAGTTGCTCAATTTCT 
               
               
                 AACATCGAAACTGTCATAGAGTTTCAGCAGAAGAACAATCGGCTCTTGGAAATAAC 
               
               
                 AAGGGAGTTTTCAGTCAACGCCGGGGTAACAACACCCGTGTCCACATACATGCTGA 
               
               
                 CAAACTCCGAGTTGCTCTCTCTTATCAACGACATGCCAATTACAAACGACCAGAAGA 
               
               
                 AATTGATGTCCAACAACGTCCAAATCGTACGACAGCAGTCTTATTCCATTATGAGTA 
               
               
                 TTATTAAGGAAGAGGTATTGGCTTATGTAGTACAACTCCCCTTGTACGGGGTAATAG 
               
               
                 ACACCCCCTGTTGGAAACTGCATACGAGTCCCCTGTGTACAACCAATACGAAGGAG 
               
               
                 GGCTCCAATATATGTTTGACAAGAACTGACCGCGGCTGGTACTGTGATAATGCTGGT 
               
               
                 AGTGTTAGCTTCTTTCCACAAGCGGAGACTTGCAAGGTACAATCTAATCGGGTTTTC 
               
               
                 TGCGATACGATGAACTCTCTGACTCTGCCGAGTGAGGTCAACCTGTGCAACGTGGAC 
               
               
                 ATATTCAATCCGAAGTACGATTGTAAAATTATGACATCCAAGACAGATGTAAGCAG 
               
               
                 CTCTGTTATTACGTCACTGGGCGCTATTGTGTCATGCTACGGTAAGACTAAATGTAC 
               
               
                 CGCATCCAATAAAAACAGGGGGATTATTAAAACCTTCAGCAACGGATGCGATTATG 
               
               
                 TCAGCAATAAGGGCGTGGATACCGTATCCGTTGGCAATACTCTCTATTACGTAAATA 
               
               
                 AACAGGAAGGCAAATCTCTCTATGTTAAAGGCGAACCTATAATCAATTTTTACGATC 
               
               
                 CGCTTGTATTCCCTTCCGATGAATTCGATGCCTCTATCTCTCAAGTTAACGAAAAAAT 
               
               
                 CAATCAATCTCTGGCATTTATTAGGAAGTCAGATGAACTCCTA 
               
               
                   
               
               
                 SEQ ID NO: 14: hCdn. RSV-HEK-Pre-F (1725 nts) 
               
               
                 ATGGAATTGCTCATTTTGAAAGCTAATGCTATAACAACAATACTCACGGCTGT 
               
               
                 AACTTTTTGCTTTGCCTCTGGTCAAAACATAACGGAAGAGTTTTATCAGTCAACGTG 
               
               
                 TTCAGCCGTATCAAAAGGGTATCTTAGCGCACTGCGCACTGGATGGTACACGTCTGT 
               
               
                 GATTACCATTGAACTCAGTAATATCAAGGAAAATAAATGCAACGGCACTGATGCAA 
               
               
                 AAGTCAAGCTCATAAAACAGGAGCTTGACAAGTACAAAAATGCGGTTACAGAACTC 
               
               
                 CAGCTCCTTATGCAATCTACCCCAGCAACCAACAACAAAGCCAAGAAGGAGCTGCC 
               
               
                 CAGGTTTATGAACTATACACTTAACAACGCGAAGAAAACCAATGTCACTCTCAGTA 
               
               
                 AAAAGAAAAAAAAGAAGTTCTTGGGGTTCCTTCTCGGTGTTGGAAGCGCCATTGCA 
               
               
                 AGCGGTGTAGCAGTTTGCAAAGTTCTCCACCTTGAGGGGGAGGTGAACAAAATTAA 
               
               
                 ATCTGCCCTCCTCTCAACTAACAAAGCCGTCGTCAGCTTGAGTAACGGCGTAAGCGT 
               
               
                 ACTCACTTTCAAAGTTCTCGATCTGAAGAACTATATTGATAAACAGCTGCTCCCAAT 
               
               
                 ACTGAACAAGCAGTCATGCAGCATCAGCAACATTGAAACCGTGATAGAGTTCCAGC 
               
               
                 AGAAAAATAATAGGCTTTTGGAGATAACTCGGGAGTTTTCAGTCAACGCGGGTGTA 
               
               
                 ACAACGCCAGTTTCCACGTATATGCTGACAAACAGTGAGCTCCTGAGCCTGATAAAT 
               
               
                 GATATGCCAATCACAAACGATCAGAAAAAACTCATGTCCAATAACGTTCAGATAGT 
               
               
                 ACGGCAACAGAGTTACAGCATAATGTGCATAATTAAAGAGGAGGTCCTGGCTTATG 
               
               
                 TTGTCCAGCTTCCACTGTACGGGGTTATAGATACCCCATGTTGGAAGCTCCATACAT 
               
               
                 CTCCCCTGTGTACTACTAACACCAAGGAGGGAAGCAATATATGTTTGACTCGCACTG 
               
               
                 ACAGGGGTTGGTACTGTGATAATGCCGGGTCCGTGAGCTTTTTTCCGCAGGCTGAAA 
               
               
                 CTTGCAAGGTGCAATCTAACCGAGTGTTCTGTGACACTATGAATTCTCTGACTCTCC 
               
               
                 CGTCAGAAGTAAACTTGTGTAATGTCGACATATTTAACCCTAAATACGATTGTAAGA 
               
               
                 TCATGACAAGCAAAACAGACGTCTCAAGTTCTGTCATAACAAGCTTGGGCGCGATT 
               
               
                 GTGTCCTGTTATGGTAAAACCAAATGCACGGCGTCCAACAAAAATAGGGGCATTAT 
               
               
                 TAAAACTTTTTCCAACGGCTGTGATTACGTCTCCAATAAAGGAGTGGATACGGTCTC 
               
               
                 AGTTGGGAATACTCTGTACTATGTTAACAAACAAGAGGGCAAGTCTCTTTATGTGAA 
               
               
                 AGGGGAACCGATTATAAACTTTTACGACCCGCTTGTGTTCCCGTCCGATGAGTTCGA 
               
               
                 TGCGAGTATTTCCCAAGTCAACGAGAAGATAAACCAGTCCCTCGCGTTTATCCGCAA 
               
               
                 AAGTGACGAGCTCCTTCATAACGTTAATGCTGGTAAGTCCACTACGAACATCATGAT 
               
               
                 CACAACAATTATCATAGTCATTATTGTTATACTGCTTAGCCTGATCGCTGTAGGGTTG 
               
               
                 CTCTTGTACTGTAAAGCGAGGTCTACCCCAGTTACCCTTAGTAAAGACCAATTGAGT 
               
               
                 GGGATCAACAACATTGCGTTTTCCAATTGA 
               
               
                   
               
               
                 SEQ ID NO: 15: RSV-NΔ3 (714 nts) 
               
               
                 CAACTTCTGTCATCCAGCAAATACACCATCCAACGGAGCACAGGAGATAGTA 
               
               
                 TTGATACTCCTAATTATGATGTGCAGAAACACATCAATAAGTTATGTGGCATGTTAT 
               
               
                 TAATCACAGAAGATGCTAATCATAAATTCACTGGGTTAATAGGTATGTTATATGCGA 
               
               
                 TGTCTAGGTTAGGAAGAGAAGACACCATAAAAATACTCAGAGATGCGGGATATCAT 
               
               
                 GTAAAAGCAAATGGAGTAGATGTAACAACACATCGTCAAGACATTAATGGAAAAGA 
               
               
                 AATGAAATTTGAAGTGTTAACATTGGCAAGCTTAACAACTGAAATTCAAATCAACAT 
               
               
                 TGAGATAGAATCTAGAAAATCCTACAAAAAAATGCTAAAAGAAATGGGAGAGGTA 
               
               
                 GCTCCAGAATACAGGCATGACTCTCCTGATTGTGGGATGATAATATTATGTATAGCA 
               
               
                 GCATTAGTAATAACTAAATTAGCAGCAGGGGACAGATCTGGTCTTACAGCCGTGATT 
               
               
                 AGGAGAGCTAATAATGTCCTAAAAAATGAAATGAAACGTTACAAAGGCTTACTACC 
               
               
                 CAAGGACATAGCCAACAGCTTCTATGAAGTGTTTGAAAAACATCCCCACTTTATAGA 
               
               
                 TGTTTTTGTTCATTTTGGTATAGCACAATCTTCTACCAGAGGTGGCAGTAGAGTTGA 
               
               
                 AGGGATTTTTGCAGGATTGTTTATGAATGCCTATGGTGCA 
               
               
                   
               
               
                 SEQ ID NO: 16: RSV-NΔ3-1 (762 nts) 
               
               
                 CAACTTCTGTCATCCAGCAAATACACCATCCAACGGAGCACAGGAGATAGTA 
               
               
                 TTGATACTCCTAATTATGATGTGCAGAAACACATCAATAAGTTATGTGGCATGTTAT 
               
               
                 TAATCACAGAAGATGCTAATCATAAATTCACTGGGTTAATAGGTATGTTATATGCGA 
               
               
                 TGTCTAGGTTAGGAAGAGAAGACACCATAAAAATACTCAGAGATGCGGGATATCAT 
               
               
                 GTAAAAGCAAATGGAGTAGATGTAACAACACATCGTCAAGACATTAATGGAAAAGA 
               
               
                 AATGAAATTTGAAGTGTTAACATTGGCAAGCTTAACAACTGAAATTCAAATCAACAT 
               
               
                 TGAGATAGAATCTAGAAAATCCTACAAAAAAATGCTAAAAGAAATGGGAGAGGTA 
               
               
                 GCTCCAGAATACAGGCATGACTCTCCTGATTGTGGGATGATAATATTATGTATAGCA 
               
               
                 GCATTAGTAATAACTAAATTAGCAGCAGGGGACAGATCTGGTCTTACAGCCGTGATT 
               
               
                 AGGAGAGCTAATAATGTCCTAAAAAATGAAATGAAACGTTACAAAGGCTTACTACC 
               
               
                 CAAGGACATAGCCAACAGCTTCTATGAAGTGTTTGAAAAACATCCCCACTTTATAGA 
               
               
                 TGTTTTTGTTCATTTTGGTATAGCACAATCTTCTACCAGAGGTGGCAGTAGAGTTGA 
               
               
                 AGGGATTTTTGCAGGATTGTTTATGAATGCCTATGGTGCAGGGCAAGTGATGTTACG 
               
               
                 GTGGGGAGTCTTAGCAAAATCAGTTAAAAAT 
               
               
                   
               
               
                 SEQ ID NO: 17: RSV-CTL-2 (213 nts) 
               
               
                 GCAGGATTCTACCATATATTGAACAACCCAAAAGCATCATTATTATCTTTGAC 
               
               
                 TCAATTTCCTCACTTCTCCAGTGTAGTATTAGGCAATGCTGCTGGCCTAGGCATAAT 
               
               
                 GGGAGAGTACAGAGGTACACCGAGGAATCAAGATCTATATGATGCAGCAAAGGCAT 
               
               
                 ATGCTGAACAACTCAAAGAAAATGGTGTGATTAACTACAGTGTACTA 
               
               
                   
               
               
                 SEQ ID NO: 18: RSV-N-CTL-4 (114 nts) 
               
               
                 TCTACCAGAGGTGGCAGTAGAGTTGAAGGGATTTTTGCAGGATTGTTTATGA 
               
               
                 ATGCCTATGGTGCAGGGCAAGTGATGTTACGGTGGGGAGTCTTAGCAAAATCAGTT 
               
               
                 AAAAAT 
               
               
                   
               
               
                 SEQ ID NO: 19: RSV-M2-1 (585 nts) 
               
               
                 ATGTCACGAAGGAATCCTTGCAAATTTGAAATTCGAGGTCATTGCTTAAATG 
               
               
                 GTAAGAGGTGTCATTTTAGTCATAATTATTTTGAATGGCCACCCCATGCACTGCTTGT 
               
               
                 AAGACAAAACTTTATGTTAAACAGAATACTTAAGTCTATGGATAAAAGTATAGATA 
               
               
                 CCTTATCAGAAATAAGTGGAGCTGCAGAGTTGGACAGAACAGAAGAGTATGCTCTT 
               
               
                 GGTGTAGTTGGAGTGCTAGAGAGTTATATAGGATCAATAAACAATATAACTAAACA 
               
               
                 ATCAGCATGTGTTGCCATGAGCAAACTCCTCACTGAACTCAATAGTGATGATATCAA 
               
               
                 AAAGCTGAGGGACAATGAAGAGCTAAATTCACCCAAGATAAGAGTGTACAATACTG 
               
               
                 TCATATCATATATTGAAAGCAACAGGAAAAACAATAAACAAACTATCCATCTGTTA 
               
               
                 AAAAGATTGCCAGCAGACGTATTGAAGAAAACCATCAAAAACACATTGGATATCCA 
               
               
                 TAAGAGCATAACCATCAACAACCCAAAAGAATCAACTGTTAGTGATACAAATGACC 
               
               
                 ATGCCAAAAATAATGATACTACCTGA 
               
               
                   
               
               
                 SEQ ID NO: 20: Human HSP-70 (1926 nts or 642 aa) 
               
               
                 ATGGCCAAAGCCGCGGCAGTCGGCATCGACCTGGGCACCACCTACTCCTGCG 
               
               
                 TGGGGGTGTTCCAACACGGCAAGGTGGAGATCATCGCCAACGACCAGGGCAACCGC 
               
               
                 ACCACCCCCAGCTACGTGGCCTTCACGGACACCGAGCGGCTCATCGGGGATGCGGC 
               
               
                 CAAGAACCAGGTGGCGCTGAACCCGCAGAACACCGTGTTTGACGCGAAGCGCCTGA 
               
               
                 TTGGCCGCAAGTTCGGCGACCCGGTGGTGCAGTCGGACATGAAGCACTGGCCTTTCC 
               
               
                 AGGTGATCAACGACGGAGACAAGCCCAAGGTGCAGGTGAGCTACAAGGGGGAGAC 
               
               
                 CAAGGCATTCTACCCCGAGGAGATCTCGTCCATGGTGCTGACCAAGATGAAGGAGA 
               
               
                 TCGCCGAGGCGTACCTGGGCTACCCGGTGACCAACGCGGTGATCACCGTGCCGGCC 
               
               
                 TACTTCAACGACTCGCAGCGCCAGGCCACCAAGGATGCGGGTGTGATCGCGGGGCT 
               
               
                 CAACGTGCTGCGGATCATCAACGAGCCCACGGCCGCCGCCATCGCCTACGGCCTGG 
               
               
                 ACAGAACGGGCAAGGGGGAGCGCAACGTGCTCATCTTTGACCTGGGCGGGGGCACC 
               
               
                 TTCGACGTGTCCATCCTGACGATCGACGACGGCATCTTCGAGGTGAAGGCCACGGCC 
               
               
                 GGGGACACCCACCTGGGTGGGGAGGACTTTGACAACAGGCTGGTGAACCACTTCGT 
               
               
                 GGAGGAGTTCAAGAGAAAACACAAGAAGGACATCAGCCAGAACAAGCGAGCCGTG 
               
               
                 AGGCGGCTGCGCACCGCCTGCGAGAGGGCCAAGAGGACCCTGTCGTCCAGCACCCA 
               
               
                 GGCCAGCCTGGAGATCGACTCCCTGTTTGAGGGCATCGACTTCTACACGTCCATCAC 
               
               
                 CAGGGCGAGGTTCGAGGAGCTGTGCTCCGACCTGTTCCGAAGCACCCTGGAGCCCG 
               
               
                 TGGAGAAGGCTCTGCGCGACGCCAAGCTGGACAAGGCCCAGATTCACGACCTGGTC 
               
               
                 CTGGTCGGGGGCTCCACCCGCATCCCCAAGGTGCAGAAGCTGCTGCAGGACTTCTTC 
               
               
                 AACGGGCGCGACCTGAACAAGAGCATCAACCCCGACGAGGCTGTGGCCTACGGGGC 
               
               
                 GGCGGTGCAGGCGGCCATCCTGATGGGGGACAAGTCCGAGAACGTGCAGGACCTGC 
               
               
                 TGCTGCTGGACGTGGCTCCCCTGTCGCTGGGGCTGGAGACGGCCGGAGGCGTGATG 
               
               
                 ACTGCCCTGATCAAGCGCAACTCCACCATCCCCACCAAGCAGACGCAGATCTTCACC 
               
               
                 ACCTACTCCGACAACCAACCCGGGGTGCTGATCCAGGTGTACGAGGGCGAGAGGGC 
               
               
                 CATGACGAAAGACAACAATCTGTTGGGGCGCTTCGAGCTGAGCGGCATCCCTCCGG 
               
               
                 CCCCCAGGGGCGTGCCCCAGATCGAGGTGACCTTCGACATCGATGCCAACGGCATC 
               
               
                 CTGAACGTCACGGCCACGGACAAGAGCACCGGCAAGGCCAACAAGATCACCATCAC 
               
               
                 CAACGACAAGGGCCGCCTGAGCAAGGAGGAGATCGAGCGCATGGTGCAGGAGGCG 
               
               
                 GAGAAGTACAAAGCGGAGGACGAGGTGCAGCGCGAGAGGGTGTCAGCCAAGAACG 
               
               
                 CCCTGGAGTCCTACGCCTTCAACATGAAGAGCGCCGTGGAGGATGAGGGGCTCAAG 
               
               
                 GGCAAGATCAGCGAGGCGGACAAGAAGAAGGTGCTGGACAAGTGTCAAGAGGTCA 
               
               
                 TCTCGTGGCTGGACGCCAACACCTTGGCCGAGAAGGACGAGTTTGAGCACAAGAGG 
               
               
                 AAGGAGCTGGAGCAGGTGTGTAACCCCATCATCAGCGGACTGTACCAGGGTGCCGG 
               
               
                 TGGTCCCGGGCCTGGGGGCTTCGGGGCTCAGGGTCCCAAGGGAGGGTCTGGGTCAG 
               
               
                 GCC CCACCATTGAGGAGGTAGATTAG 
               
               
                   
               
               
                 Sequence to express RSV-G and F genes in tandem 
               
               
                 SEQ ID NO: 21: hCdn. RSV G-2A-F (2682 nts) (G and F genes 
               
               
                 separated by 2A peptide sequence) 
               
               
                 ATGTCCAAAAACAAGGATCAACGAACGGCTAAAACACTGGAAAGAACTTGG 
               
               
                 GATACTCTTAATCACCTTCTTTTCATCAGCTCCTGTTTGTATAAGTTGAACTTGAAAA 
               
               
                 GTGTAGCACAAATTACCTTGTCAATTCTGGCTATGATTATTTCCACTAGTTTGATCAT 
               
               
                 TGCTGCGATTATATTTATTGCTTCTGCAAATCATAAGGTAACCCCGACTACAGCGAT 
               
               
                 CATTCAGGACGCTACAAGTCAAATAAAGAACACCACACCGACGTACTTGACCCAGA 
               
               
                 ATCCCCAGCTTGGCATCAGTCCTTCTAACCCTTCTGAAATCACCTCCCAAATCACCA 
               
               
                 CTATCCTTGCGTCTACCACACCTGGAGTAAAGAGTACATTGCAGTCTACTACCGTTA 
               
               
                 AGACCAAGAACACAACCACAACTCAAACGCAGCCATCTAAGCCAACTACCAAACAG 
               
               
                 CGGCAAAATAAACCTCCATCTAAACCGAATAACGATTTTCACTTTGAAGTATTCAAC 
               
               
                 TTTGTTCCCTGCTCAATTTGCAGCAATAATCCGACCTGCTGGGCTATATGTAAGCGG 
               
               
                 ATACCAAATAAAAAGCCAGGAAAGAAAACTACAACAAAACCTACGAAGAAGCCTA 
               
               
                 CACTGAAGACCACAAAAAAAGACCCAAAACCCCAGACAACCAAGTCCAAGGAAGT 
               
               
                 TCCCACTACTAAGCCCACTGAAGAGCCTACCATAAATACCACCAAGACAAACATCA 
               
               
                 TAACCACCTTGCTCACCTCTAATACTACCGGAAACCCTGAGCTCACTTCCCAAATGG 
               
               
                 AAACGTTCCATTCAACTAGTAGTGAGGGCAACCCGAGTCCCAGCCAGGTCTCTACA 
               
               
                 ACCTCAGAATACCCCTCCCAACCTAGTTCACCCCCAAATACTCCACGGCAGGGATCC 
               
               
                 GGAGAGGGAAGAGGAAGTTTGCTGACATGTGGAGATGTGGAGGAAAATCCCGGTCC 
               
               
                 AATGGAGCTTCTGATCCTGAAAGCTAACGCTATTACTACTATACTTACCGCCGTAAC 
               
               
                 ATTCTGCTTCGCCTCCGGACAAAACATCACAGAAGAGTTCTATCAATCCACGTGCAG 
               
               
                 CGCTGTGTCTAAGGGCTATCTGAGCGCATTGAGAACGGGGTGGTATACTTCCGTAAT 
               
               
                 TACTATAGAGCTGTCAAACATTAAGAAAAACAAGTGTAACGGTACCGACGCTAAAG 
               
               
                 TAAAGCTCATCAAGCAGGAGCTGGATAAATACAAAAATGCTGTCACTGAACTCCAG 
               
               
                 CTTCTTATGCAATCTACCCAAGCAACCAACAACCGGGCTAGGCGCGAATTGCCCAG 
               
               
                 GTTCATGAATTATACATTGAACAACGCCAAAAAGACTAATGTAACCCTCAGCAAGA 
               
               
                 AACGCAAGAGGCGGTTCCTGGGATTTCTTCTCGGAGTAGGTTCCGCTATAGCGTCCG 
               
               
                 GAGTAGCGGTCTCAAAAGTATTGCATCTGGAAGGCGAAGTTAACAAAATTAAGAGC 
               
               
                 GCGCTCCTCAGCACCAACAAGGCGGTAGTCAGCCTCAGCAACGGCGTATCTGTTCTC 
               
               
                 ACATCTAAAGTTTTGGACCTGAAAAACTATATAGACAAGCAGTTGCTTCCGATAGTA 
               
               
                 AATAAGCAATCATGTTCCATTTCAAACATAGAAACGGTTATCGAGTTTCAACAGAAA 
               
               
                 AATAATAGATTGCTTGAGATCACAAGAGAGTTCTCTGTCAATGCAGGTGTGACTACG 
               
               
                 CCGGTCAGCACATATATGCTCACGAATAGTGAACTGCTGAGTCTTATAAATGATATG 
               
               
                 CCGATTACTAATGACCAAAAAAAGCTCATGAGCAACAATGTCCAAATCGTTCGACA 
               
               
                 ACAAAGTTACTCTATCATGAGCATCATCAAAGAGGAGGTTCTCGCATATGTCGTGCA 
               
               
                 GCTTCCGTTGTATGGTGTAATAGATACCCCGTGCTGGAAGCTGCACACCTCTCCACT 
               
               
                 GTGCACAACCAATACTAAAGAGGGGTCTAATATCTGTCTCACGAGAACGGATCGAG 
               
               
                 GATGGTACTGCGATAACGCCGGTAGTGTGAGCTTCTTCCCCCAGGCTGAAACCTGTA 
               
               
                 AGGTACAGAGTAACAGGGTATTCTGTGACACTATGAACTCACTCACACTGCCAAGT 
               
               
                 GAAGTGAACCTTTGTAACGTTGACATATTTAATCCCAAGTACGACTGCAAAATCATG 
               
               
                 ACAAGCAAAACCGACGTTTCCTCAAGCGTCATAACGAGTTTGGGTGCTATAGTAAGT 
               
               
                 TGCTATGGGAAAACCAAGTGCACGGCATCCAATAAGAACAGAGGGATCATAAAAAC 
               
               
                 GTTCTCCAACGGATGTGACTATGTGTCAAACAAGGGGGTTGATACGGTATCAGTTGG 
               
               
                 AAATACCCTTTATTATGTCAACAAGCAGGAAGGAAAGAGCCTCTATGTAAAAGGCG 
               
               
                 AACCCATAATCAATTTTTATGACCCACTCGTATTCCCTAGTGATGAGTTCGATGCCTC 
               
               
                 TATTAGCCAGGTAAATGAGAAGATCAACCAGAGTTTGGCCTTTATCCGCAAATCTGA 
               
               
                 CGAGCTGCTCCATAATGTCAATGCAGGGAAAAGTACGACTAATATCATGATTACTAC 
               
               
                 GATTATTATCGTCATCATCGTCATCCTCTTGAGTCTTATAGCGGTAGGGCTCCTGCTC 
               
               
                 TACTGTAAAGCGCGCTCTACCCCTGTGACGCTGTCCAAAGATCAACTTTCTGGCATA 
               
               
                 AACAACATTGCCTTTAGTAATTAA 
               
               
                   
               
               
                 SEQ ID NO: 22: VSV (Indiana strain) 
               
               
                 ACGAAGACAAACAAACCATTATTATCATTAAAAGGCTCAGGAGAAACTTTAA 
               
               
                 CAGTAATCAAAATGTCTGTTACAGTCAAGAGAATCATTGACAACACAGTCATAGTTC 
               
               
                 CAAAACTTCCTGCAAATGAGGATCCAGTGGAATACCCGGCAGATTACTTCAGAAAA 
               
               
                 TCAAAGGAGATTCCTCTTTACATCAATACTACAAAAAGTTTGTCAGATCTAAGAGGA 
               
               
                 TATGTCTACCAAGGCCTCAAATCCGGAAATGTATCAATCATACATGTCAACAGCTAC 
               
               
                 TTGTATGGAGCATTAAAGGACATCCGGGGTAAGTTGGATAAAGATTGGTCAAGTTTC 
               
               
                 GGAATAAACATCGGGAAAGCAGGGGATACAATCGGAATATTTGACCTTGTATCCTT 
               
               
                 GAAAGCCCTGGACGGCGTACTTCCAGATGGAGTATCGGATGCTTCCAGAACCAGCG 
               
               
                 CAGATGACAAATGGTTGCCTTTGTATCTACTTGGCTTATACAGAGTGGGCAGAACAC 
               
               
                 AAATGCCTGAATACAGAAAAAAGCTCATGGATGGGCTGACAAATCAATGCAAAATG 
               
               
                 ATCAATGAACAGTTTGAACCTCTTGTGCCAGAAGGTCGTGACATTTTTGATGTGTGG 
               
               
                 GGAAATGACAGTAATTACACAAAAATTGTCGCTGCAGTGGACATGTTCTTCCACATG 
               
               
                 TTCAAAAAACATGAATGTGCCTCGTTCAGATACGGAACTATTGTTTCCAGATTCAAA 
               
               
                 GATTGTGCTGCATTGGCAACATTTGGACACCTCTGCAAAATAACCGGAATGTCTACA 
               
               
                 GAAGATGTAACGACCTGGATCTTGAACCGAGAAGTTGCAGATGAAATGGTCCAAAT 
               
               
                 GATGCTTCCAGGCCAAGAAATTGACAAGGCCGATTCATACATGCCTTATTTGATCGA 
               
               
                 CTTTGGATTGTCTTCTAAGTCTCCATATTCTTCCGTCAAAAACCCTGCCTTCCACTTC 
               
               
                 TGGGGGCAATTGACAGCTCTTCTGCTCAGATCCACCAGAGCAAGGAATGCCCGACA 
               
               
                 GCCTGATGACATTGAGTATACATCTCTTACTACAGCAGGTTTGTTGTACGCTTATGC 
               
               
                 AGTAGGATCCTCTGCCGACTTGGCACAACAGTTTTGTGTTGGAGATAACAAATACAC 
               
               
                 TCCAGATGATAGTACCGGAGGATTGACGACTAATGCACCGCCACAAGGCAGAGATG 
               
               
                 TGGTCGAATGGCTCGGATGGTTTGAAGATCAAAACAGAAAACCGACTCCTGATATG 
               
               
                 ATGCAGTATGCGAAAAGAGCAGTCATGTCACTGCAAGGCCTAAGAGAGAAGACAAT 
               
               
                 TGGCAAGTATGCTAAGTCAGAATTTGACAAATGACCCTATAATTCTCAGATCACCTA 
               
               
                 TTATATATTATGCTACATATGAAAAAAACTAACAGATATCATGGATAATCTCACAAA 
               
               
                 AGTTCGTGAGTATCTCAAGTCCTACTCTCGTCTAGATCAGGCGGTAGGAGAGATAGA 
               
               
                 TGAGATCGAAGCACAACGAGCTGAAAAGTCCAATTATGAGTTGTTCCAAGAGGACG 
               
               
                 GAGTGGAAGAGCATACTAGGCCCTCTTATTTTCAGGCAGCAGATGATTCTGACACAG 
               
               
                 AATCTGAACCAGAAATTGAAGACAATCAAGGCTTGTATGTACCAGATCCGGAAGCT 
               
               
                 GAGCAAGTTGAAGGCTTTATACAGGGGCCTTTAGATGACTATGCAGATGAGGACGT 
               
               
                 GGATGTTGTATTCACTTCGGACTGGAAACAGCCTGAGCTTGAATCCGACGAGCATGG 
               
               
                 AAAGACCTTACGGTTGACATTGCCAGAGGGTTTAAGTGGAGAGCAGAAATCCCAGT 
               
               
                 GGCTTTTGACGATTAAAGCAGTCGTTCAAAGTGCCAAACACTGGAATCTGGCAGAG 
               
               
                 TGCACATTTGAAGCATCGGGAGAAGGGGTCATCATAAAAAAGCGCCAGATAACTCC 
               
               
                 GGATGTATATAAGGTCACTCCAGTGATGAACACACATCCGTACCAATCAGAAGCCG 
               
               
                 TATCAGATGTTTGGTCTCTCTCAAAGACATCCATGACTTTCCAACCCAAGAAAGCAA 
               
               
                 GTCTTCAGCCTCTCACCATATCCTTGGATGAATTGTTCTCATCTAGAGGAGAATTCAT 
               
               
                 CTCTGTCGGAGGTAACGGACGAATGTCTCATAAAGAGGCCATCCTGCTCGGTCTGAG 
               
               
                 GTACAAAAAGTTGTACAATCAGGCGAGAGTCAAATATTCTCTGTAGACTATGAAAA 
               
               
                 AAAGTAACAGATATCACAATCTAAGTGTTATCCCAATCCATTCATCATGAGTTCCTT 
               
               
                 AAAGAAGATTCTCGGTCTGAAGGGGAAAGGTAAGAAATCTAAGAAATTAGGGATCG 
               
               
                 CACCACCCCCTTATGAAGAGGACACTAGCATGGAGTATGCTCCGAGCGCTCCAATTG 
               
               
                 ACAAATCCTATTTTGGAGTTGACGAGATGGACACCTATGATCCGAATCAATTAAGAT 
               
               
                 ATGAGAAATTCTTCTTTACAGTGAAAATGACGGTTAGATCTAATCGTCCGTTCAGAA 
               
               
                 CATACTCAGATGTGGCAGCCGCTGTATCCCATTGGGATCACATGTACATCGGAATGG 
               
               
                 CAGGGAAACGTCCCTTCTACAAAATCTTGGCTTTTTTGGGTTCTTCTAATCTAAAGGC 
               
               
                 CACTCCAGCGGTATTGGCAGATCAAGGTCAACCAGAGTATCACGCTCACTGCGAAG 
               
               
                 GCAGGGCTTATTTGCCACATAGGATGGGGAAGACCCCTCCCATGCTCAATGTACCAG 
               
               
                 AGCACTTCAGAAGACCATTCAATATAGGTCTTTACAAGGGAACGATTGAGCTCACA 
               
               
                 ATGACCATCTACGATGATGAGTCACTGGAAGCAGCTCCTATGATCTGGGATCATTTC 
               
               
                 AATTCTTCCAAATTTTCTGATTTCAGAGAGAAGGCCTTAATGTTTGGCCTGATTGTCG 
               
               
                 AGAAAAAGGCATCTGGAGCGTGGGTCCTGGATTCTATCAGCCACTTCAAATGAGCT 
               
               
                 AGTCTAGCTTCCAGCTTCTGAACAATCCCCGGTTTACTCAGTCTCTCCTAATTCCAGC 
               
               
                 CTTTCGAACAACTAATATCCTGTCTTTTCTATCCCTATGAAAAAAACTAACAGAGAT 
               
               
                 CGATCTGTTTCCTTGACACCATGAAGTGCCTTTTGTACTTAGCTTTTTTATTCATCGG 
               
               
                 GGTGAATTGCAAGTTCACCATAGTTTTTCCACACAACCGAAAAGGAAACTGGAAAA 
               
               
                 ATGTTCCTTCCAATTACCATTATTGCCCGTCAAGCTCAGATTTAAATTGGCATAATGA 
               
               
                 CTTAATAGGCACAGCCTTACAAGTCAAAATGCCCAAGAGTCACAAGGCTATTCAAG 
               
               
                 CAGACGGTTGGATGTGTCATGCTTCCAAATGGGTCACTACTTGTGATTTCCGCTGGT 
               
               
                 ACGGACCGGAGTATATAACACATTCCATCCGATCCTTCACTCCATCTGTAGAACAAT 
               
               
                 GCAAGGAAAGCATTGAACAAACGAAACAAGGAACTTGGCTGAATCCAGGCTTCCCT 
               
               
                 CCTCAAAGTTGTGGATATGCAACTGTGACGGATGCTGAAGCAGCGATTGTCCAGGT 
               
               
                 GACTCCTCACCATGTGCTTGTTGATGAATACACAGGAGAATGGGTTGATTCACAGTT 
               
               
                 CATCAACGGAAAATGCAGCAATGACATATGCCCCACTGTCCATAACTCCACAACCT 
               
               
                 GGCATTCCGACTATAAGGTCAAAGGGCTATGTGATTCTAACCTCATTTCCATGGACA 
               
               
                 TCACCTTCTTCTCAGAGGACGGAGAGCTATCATCCCTAGGAAAGGAGGGCACAGGG 
               
               
                 TTCAGAAGTAACTACTTTGCTTATGAAACTGGAGACAAGGCCTGCAAAATGCAGTA 
               
               
                 CTGCAAGCATTGGGGAGTCAGACTCCCATCAGGTGTCTGGTTCGAGATGGCTGATAA 
               
               
                 GGATCTCTTTGCTGCAGCCAGATTCCCTGAATGCCCAGAAGGGTCAAGTATCTCTGC 
               
               
                 TCCATCTCAGACCTCAGTGGATGTAAGTCTCATTCAGGACGTTGAGAGGATCTTGGA 
               
               
                 TTATTCCCTCTGCCAAGAAACCTGGAGCAAAATCAGAGCGGGTCTTCCCATCTCTCC 
               
               
                 AGTGGATCTCAGCTATCTTGCTCCTAAAAACCCAGGAACCGGTCCTGTCTTTACCAT 
               
               
                 AATCAATGGTACCCTAAAATACTTTGAGACCAGATACATCAGAGTCGATATTGCTGC 
               
               
                 TCCAATCCTCTCAAGAATGGTCGGAATGATCAGTGGAACTACCACAGAAAGGGAAC 
               
               
                 TGTGGGATGACTGGGCTCCATATGAAGACGTGGAAATTGGACCCAATGGAGTTCTG 
               
               
                 AGGACCAGTTCAGGATATAAGTTTCCTTTATATATGATTGGACATGGTATGTTGGAC 
               
               
                 TCCGATCTTCATCTTAGCTCAAAGGCTCAGGTGTTTGAACATCCTCACATTCAAGAC 
               
               
                 GCTGCTTCGCAGCTTCCTGATGATGAGACTTTATTTTTTGGTGATACTGGGCTATCCA 
               
               
                 AAAATCCAATCGAGTTTGTAGAAGGTTGGTTCAGTAGTTGGAAGAGCTCTATTGCCT 
               
               
                 CTTTTTGCTTTATCATAGGGTTAATCATTGGACTATTCTTGGTTCTCCGAGTTGGTAT 
               
               
                 TTATCTTTGCATTAAATTAAAGCACACCAAGAAAAGACAGATTTATACAGACATAG 
               
               
                 AGATGAACCGACTTGGAAAGTAACTCAAATCCTGCACAACAGATTCTTCATGTTTGA 
               
               
                 ACCAAATCAACTTGTGATATCATGCTCAAAGAGGCCTTAATTATATTTTAATTTTTAA 
               
               
                 TTTTTATGAAAAAAACTAACAGCAATCATGGAAGTCCACGATTTTGAGACCGACGA 
               
               
                 GTTCAATGATTTCAATGAAGATGACTATGCCACAAGAGAATTCCTGAATCCCGATGA 
               
               
                 GCGCATGACGTACTTGAATCATGCTGATTACAATTTGAATTCTCCTCTAATTAGTGAT 
               
               
                 GATATTGACAATTTGATCAGGAAATTCAATTCTCTTCCGATTCCCTCGATGTGGGAT 
               
               
                 AGTAAGAACTGGGATGGAGTTCTTGAGATGTTAACATCATGTCAAGCCAATCCCATC 
               
               
                 TCAACATCTCAGATGCATAAATGGATGGGAAGTTGGTTAATGTCTGATAATCATGAT 
               
               
                 GCCAGTCAAGGGTATAGTTTTTTACATGAAGTGGACAAAGAGGCAGAAATAACATT 
               
               
                 TGACGTGGTGGAGACCTTCATCCGCGGCTGGGGCAACAAACCAATTGAATACATCA 
               
               
                 AAAAGGAAAGATGGACTGACTCATTCAAAATTCTCGCTTATTTGTGTCAAAAGTTTT 
               
               
                 TGGACTTACACAAGTTGACATTAATCTTAAATGCTGTCTCTGAGGTGGAATTGCTCA 
               
               
                 ACTTGGCGAGGACTTTCAAAGGCAAAGTCAGAAGAAGTTCTCATGGAACGAACATA 
               
               
                 TGCAGGATTAGGGTTCCCAGCTTGGGTCCTACTTTTATTTCAGAAGGATGGGCTTAC 
               
               
                 TTCAAGAAACTTGATATTCTAATGGACCGAAACTTTCTGTTAATGGTCAAAGATGTG 
               
               
                 ATTATAGGGAGGATGCAAACGGTGCTATCCATGGTATGTAGAATAGACAACCTGTT 
               
               
                 CTCAGAGCAAGACATCTTCTCCCTTCTAAATATCTACAGAATTGGAGATAAAATTGT 
               
               
                 GGAGAGGCAGGGAAATTTTTCTTATGACTTGATTAAAATGGTGGAACCGATATGCA 
               
               
                 ACTTGAAGCTGATGAAATTAGCAAGAGAATCAAGGCCTTTAGTCCCACAATTCCCTC 
               
               
                 ATTTTGAAAATCATATCAAGACTTCTGTTGATGAAGGGGCAAAAATTGACCGAGGT 
               
               
                 ATAAGATTCCTCCATGATCAGATAATGAGTGTGAAAACAGTGGATCTCACACTGGTG 
               
               
                 ATTTATGGATCGTTCAGACATTGGGGTCATCCTTTTATAGATTATTACACTGGACTAG 
               
               
                 AAAAATTACATTCCCAAGTAACCATGAAGAAAGATATTGATGTGTCATATGCAAAA 
               
               
                 GCACTTGCAAGTGATTTAGCTCGGATTGTTCTATTTCAACAGTTCAATGATCATAAA 
               
               
                 AAGTGGTTCGTGAATGGAGACTTGCTCCCTCATGATCATCCCTTTAAAAGTCATGTT 
               
               
                 AAAGAAAATACATGGCCCACAGCTGCTCAAGTTCAAGATTTTGGAGATAAATGGCA 
               
               
                 TGAACTTCCGCTGATTAAATGTTTTGAAATACCCGACTTACTAGACCCATCGATAAT 
               
               
                 ATACTCTGACAAAAGTCATTCAATGAATAGGTCAGAGGTGTTGAAACATGTCCGAA 
               
               
                 TGAATCCGAACACTCCTATCCCTAGTAAAAAGGTGTTGCAGACTATGTTGGACACAA 
               
               
                 AGGCTACCAATTGGAAAGAATTTCTTAAAGAGATTGATGAGAAGGGCTTAGATGAT 
               
               
                 GATGATCTAATTATTGGTCTTAAAGGAAAGGAGAGGGAACTGAAGTTGGCAGGTAG 
               
               
                 ATTTTTCTCCCTAATGTCTTGGAAATTGCGAGAATACTTTGTAATTACCGAATATTTG 
               
               
                 ATAAAGACTCATTTCGTCCCTATGTTTAAAGGCCTGACAATGGCGGACGATCTAACT 
               
               
                 GCAGTCATTAAAAAGATGTTAGATTCCTCATCCGGCCAAGGATTGAAGTCATATGAG 
               
               
                 GCAATTTGCATAGCCAATCACATTGATTACGAAAAATGGAATAACCACCAAAGGAA 
               
               
                 GTTATCAAACGGCCCAGTGTTCCGAGTTATGGGCCAGTTCTTAGGTTATCCATCCTT 
               
               
                 AATCGAGAGAACTCATGAATTTTTTGAGAAAAGTCTTATATACTACAATGGAAGACC 
               
               
                 AGACTTGATGCGTGTTCACAACAACACACTGATCAATTCAACCTCCCAACGAGTTTG 
               
               
                 TTGGCAAGGACAAGAGGGTGGACTGGAAGGTCTACGGCAAAAAGGATGGAGTATC 
               
               
                 CTCAATCTACTGGTTATTCAAAGAGAGGCTAAAATCAGAAACACTGCTGTCAAAGTC 
               
               
                 TTGGCACAAGGTGATAATCAAGTTATTTGCACACAGTATAAAACGAAGAAATCGAG 
               
               
                 AAACGTTGTAGAATTACAGGGTGCTCTCAATCAAATGGTTTCTAATAATGAGAAAAT 
               
               
                 TATGACTGCAATCAAAATAGGGACAGGGAAGTTAGGACTTTTGATAAATGACGATG 
               
               
                 AGACTATGCAATCTGCAGATTACTTGAATTATGGAAAAATACCGATTTTCCGTGGAG 
               
               
                 TGATTAGAGGGTTAGAGACCAAGAGATGGTCACGAGTGACTTGTGTCACCAATGAC 
               
               
                 CAAATACCCACTTGTGCTAATATAATGAGCTCAGTTTCCACAAATGCTCTCACCGTA 
               
               
                 GCTCATTTTGCTGAGAACCCAATCAATGCCATGATACAGTACAATTATTTTGGGACA 
               
               
                 TTTGCTAGACTCTTGTTGATGATGCATGATCCTGCTCTTCGTCAATCATTGTATGAAG 
               
               
                 TTCAAGATAAGATACCGGGCTTGCACAGTTCTACTTTCAAATACGCCATGTTGTATT 
               
               
                 TGGACCCTTCCATTGGAGGAGTGTCGGGCATGTCTTTGTCCAGGTTTTTGATTAGAG 
               
               
                 CCTTCCCAGATCCCGTAACAGAAAGTCTCTCATTCTGGAGATTCATCCATGTACATG 
               
               
                 CTCGAAGTGAGCATCTGAAGGAGATGAGTGCAGTATTTGGAAACCCCGAGATAGCC 
               
               
                 AAGTTTCGAATAACTCACATAGACAAGCTAGTAGAAGATCCAACCTCTCTGAACATC 
               
               
                 GCTATGGGAATGAGTCCAGCGAACTTGTTAAAGACTGAGGTTAAAAAATGCTTAAT 
               
               
                 CGAATCAAGACAAACCATCAGGAACCAGGTGATTAAGGATGCAACCATATATTTGT 
               
               
                 ATCATGAAGAGGATCGGCTCAGAAGTTTCTTATGGTCAATAAATCCTCTGTTCCCTA 
               
               
                 GATTTTTAAGTGAATTCAAATCAGGCACTTTTTTGGGAGTCGCAGACGGGCTCATCA 
               
               
                 GTCTATTTCAAAATTCTCGTACTATTCGGAACTCCTTTAAGAAAAAGTATCATAGGG 
               
               
                 AATTGGATGATTTGATTGTGAGGAGTGAGGTATCCTCTTTGACACATTTAGGGAAAC 
               
               
                 TTCATTTGAGAAGGGGATCATGTAAAATGTGGACATGTTCAGCTACTCATGCTGACA 
               
               
                 CATTAAGATACAAATCCTGGGGCCGTACAGTTATTGGGACAACTGTACCCCATCCAT 
               
               
                 TAGAAATGTTGGGTCCACAACATCGAAAAGAGACTCCTTGTGCACCATGTAACACA 
               
               
                 TCAGGGTTCAATTATGTTTCTGTGCATTGTCCAGACGGGATCCATGACGTCTTTAGTT 
               
               
                 CACGGGGACCATTGCCTGCTTATCTAGGGTCTAAAACATCTGAATCTACATCTATTT 
               
               
                 TGCAGCCTTGGGAAAGGGAAAGCAAAGTCCCACTGATTAAAAGAGCTACACGTCTT 
               
               
                 AGAGATGCTATCTCTTGGTTTGTTGAACCCGACTCTAAACTAGCAATGACTATACTT 
               
               
                 TCTAACATCCACTCTTTAACAGGCGAAGAATGGACCAAAAGGCAGCATGGGTTCAA 
               
               
                 AAGAACAGGGTCTGCCCTTCATAGGTTTTCGACATCTCGGATGAGCCATGGTGGGTT 
               
               
                 CGCATCTCAGAGCACTGCAGCATTGACCAGGTTGATGGCAACTACAGACACCATGA 
               
               
                 GGGATCTGGGAGATCAGAATTTCGACTTTTTATTCCAAGCAACGTTGCTCTATGCTC 
               
               
                 AAATTACCACCACTGTTGCAAGAGACGGATGGATCACCAGTTGTACAGATCATTATC 
               
               
                 ATATTGCCTGTAAGTCCTGTTTGAGACCCATAGAAGAGATCACCCTGGACTCAAGTA 
               
               
                 TGGACTACACGCCCCCAGATGTATCCCATGTGCTGAAGACATGGAGGAATGGGGAA 
               
               
                 GGTTCGTGGGGACAAGAGATAAAACAGATCTATCCTTTAGAAGGGAATTGGAAGAA 
               
               
                 TTTAGCACCTGCTGAGCAATCCTATCAAGTCGGCAGATGTATAGGTTTTCTATATGG 
               
               
                 AGACTTGGCGTATAGAAAATCTACTCATGCCGAGGACAGTTCTCTATTTCCTCTATC 
               
               
                 TATACAAGGTCGTATTAGAGGTCGAGGTTTCTTAAAAGGGTTGCTAGACGGATTAAT 
               
               
                 GAGAGCAAGTTGCTGCCAAGTAATACACCGGAGAAGTCTGGCTCATTTGAAGAGGC 
               
               
                 CGGCCAACGCAGTGTACGGAGGTTTGATTTACTTGATTGATAAATTGAGTGTATCAC 
               
               
                 CTCCATTCCTTTCTCTTACTAGATCAGGACCTATTAGAGACGAATTAGAAACGATTC 
               
               
                 CCCACAAGATCCCAACCTCCTATCCGACAAGCAACCGTGATATGGGGGTGATTGTCA 
               
               
                 GAAATTACTTCAAATACCAATGCCGTCTAATTGAAAAGGGAAAATACAGATCACAT 
               
               
                 TATTCACAATTATGGTTATTCTCAGATGTCTTATCCATAGACTTCATTGGACCATTCT 
               
               
                 CTATTTCCACCACCCTCTTGCAAATCCTATACAAGCCATTTTTATCTGGGAAAGATA 
               
               
                 AGAATGAGTTGAGAGAGCTGGCAAATCTTTCTTCATTGCTAAGATCAGGAGAGGGG 
               
               
                 TGGGAAGACATACATGTGAAATTCTTCACCAAGGACATATTATTGTGTCCAGAGGA 
               
               
                 AATCAGACATGCTTGCAAGTTCGGGATTGCTAAGGATAATAATAAAGACATGAGCT 
               
               
                 ATCCCCCTTGGGGAAGGGAATCCAGAGGGACAATTACAACAATCCCTGTTTATTATA 
               
               
                 CGACCACCCCTTACCCAAAGATGCTAGAGATGCCTCCAAGAATCCAAAATCCCCTGC 
               
               
                 TGTCCGGAATCAGGTTGGGCCAATTACCAACTGGCGCTCATTATAAAATTCGGAGTA 
               
               
                 TATTACATGGAATGGGAATCCATTACAGGGACTTCTTGAGTTGTGGAGACGGCTCCG 
               
               
                 GAGGGATGACTGCTGCATTACTACGAGAAAATGTGCATAGCAGAGGAATATTCAAT 
               
               
                 AGTCTGTTAGAATTATCAGGGTCAGTCATGCGAGGCGCCTCTCCTGAGCCCCCCAGT 
               
               
                 GCCCTAGAAACTTTAGGAGGAGATAAATCGAGATGTGTAAATGGTGAAACATGTTG 
               
               
                 GGAATATCCATCTGACTTATGTGACCCAAGGACTTGGGACTATTTCCTCCGACTCAA 
               
               
                 AGCAGGCTTGGGGCTTCAAATTGATTTAATTGTAATGGATATGGAAGTTCGGGATTC 
               
               
                 TTCTACTAGCCTGAAAATTGAGACGAATGTTAGAAATTATGTGCACCGGATTTTGGA 
               
               
                 TGAGCAAGGAGTTTTAATCTACAAGACTTATGGAACATATATTTGTGAGAGCGAAA 
               
               
                 AGAATGCAGTAACAATCCTTGGTCCCATGTTCAAGACGGTCGACTTAGTTCAAACAG 
               
               
                 AATTTAGTAGTTCTCAAACGTCTGAAGTATATATGGTATGTAAAGGTTTGAAGAAAT 
               
               
                 TAATCGATGAACCCAATCCCGATTGGTCTTCCATCAATGAATCCTGGAAAAACCTGT 
               
               
                 ACGCATTCCAGTCATCAGAACAGGAATTTGCCAGAGCAAAGAAGGTTAGTACATAC 
               
               
                 TTTACCTTGACAGGTATTCCCTCCCAATTCATTCCTGATCCTTTTGTAAACATTGAGA 
               
               
                 CTATGCTACAAATATTCGGAGTACCCACGGGTGTGTCTCATGCGGCTGCCTTAAAAT 
               
               
                 CATCTGATAGACCTGCAGATTTATTGACCATTAGCCTTTTTTATATGGCGATTATATC 
               
               
                 GTATTATAACATCAATCATATCAGAGTAGGACCGATACCTCCGAACCCCCCATCAGA 
               
               
                 TGGAATTGCACAAAATGTGGGGATCGCTATAACTGGTATAAGCTTTTGGCTGAGTTT 
               
               
                 GATGGAGAAAGACATTCCACTATATCAACAGTGTTTGGCAGTTATCCAGCAATCATT 
               
               
                 TCCGATTAGGTGGGAGGCTATTTCAGTAAAAGGAGGATACAAGCAGAAGTGGAGTA 
               
               
                 CTAGAGGTGATGGGCTCCCAAAAGATACCCGAATTTCAGACTCCTTGGCCCCAATCG 
               
               
                 GGAACTGGATCAGATCTTTGGAATTGGTCCGAAACCAAGTTCGTCTAAATCCATTCA 
               
               
                 ATAAGATCTTGTTCAATCAGCTATGTCGTACAGTGGATAATCATTTGAAGTGGTCAA 
               
               
                 ATTTGCGAAAAAACACAGGAATGATTGAATGGATCAATGGGCGAATTTCAAAAGAA 
               
               
                 GACCGGTCTATACTGATGTTGAAGAGTGACCTACATGAGGAAAACTCTTGGAGAGA 
               
               
                 TTAAAAAATCAGGAGGAGACTCCAAACTTTAAGTATGAAAAAAACTTTGATCCTTA 
               
               
                 AGACCCTCTTGTGGTTTTTATTTTTTTATCTGGTTTTGTGGTCTTCGT