Abstract:
The present invention relates to the use of selected polypeptides from African Swine virus for the prevention and therapy of African Swine infections as well as other infections, including immune deficiencies in mammals and humans.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention generally relates to the use of selected polypeptides from African Swine virus for the prevention and therapy of African Swine infections as well as other infections, including immune deficiencies in mammals and humans. 
       BACKGROUND OF THE INVENTION 
       [0002]    African Swine fever is an endemic disease in sub-Saharan Africa and many other parts of the developing world. It is caused by the African Swine virus that primarily replicates in macrophages and monocytes leading to the impairment of the structure and function of the immune system of the infected organisms. Until now the African Swine epidemic continues to spread despite all efforts to contain it. Thus, there is an objective need for effective, safe and affordable preventive and therapeutic approaches, in particular for effective vaccines, to control and eventually eradicate this disease. 
         [0003]    Since the characteristic feature of the African Swine virus is to impair the immune system and to cause immune deficiencies in its hosts the development of vaccines and other therapeutic approaches against the African Swine virus has implications for other immune deficiencies or diseases. Several other viruses are also known to cause immunodeficiency-like syndromes in humans, including cytomegalovirus, Epstein Barr Virus and others. Moreover, a series of cases of so-called “idiopathic” immunodeficiencies have been documented that display CD4+ T-lymphocytopenia with opportunistic infections, but show no evidence of HIV infection (1). 
         [0004]    Since antibodies for the African Swine virus have been detected in humans, the possibility of human infection with the African Swine virus exists and may thus far have escaped any systematic screening. Thus, any preventive and therapeutic approach to African Swine fever can have far-reaching implications to control immune deficiency conditions in humans. 
       SUMMARY OF THE INVENTION 
       [0005]    Synthetic oligopeptides prepared from African Swine virus proteins are effective in prevention, treatment and diagnosis of African Swine fever as well as for immune deficiencies in humans. 
         [0006]    Oligopeptides are identified and selected by means of suitable algorithms from the known amino acid sequence of pathogenicity-mediating African Swine virus proteins. Subsequently, these oligopeptides are tested in vitro for their ability to decrease or completely block infection by the African Swine virus (prevention and therapy) or for their ability to raise antibodies to detect the virus (diagnosis). Ultimately, the successfully tested African Swine oligopeptides can be used in veterinary and clinical medicine. 
         [0007]    Accordingly, in one aspect, the invention provides Oligopeptides selected from the group consisting of SEQ ID NO: 1 through SEQ ID NO: 111. 
         [0008]    In one embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by omitting one or several predetermined amino residues at the N-terminal end. 
         [0009]    In another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by omitting one or several predetermined amino acid residues at the C-terminal end. 
         [0010]    In other embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by omitting one or several predetermined amino acid residues at the N-terminal and the C-terminal end. 
         [0011]    In yet another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by substituting one or several predetermined amino acid residues within the given sequence without consideration of charge and polarity of the substitution residue. 
         [0012]    In still another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by substituting one or several predetermined of the amino acid residues 
         [0013]    In one embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by omitting one or several predetermined amino acid residues within the given sequence. 
         [0014]    In another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by repeating the oligopeptides sequence one or more times each of them covalently bound to one or several predetermined oligopeptides repeat(s) with linear topology or other peptidomemetic. 
         [0015]    In yet other embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by using cyclic oligopeptide topology instead of linear oligopeptide topology or other peptidomemetic. 
         [0016]    In yet another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 are modified by repeating the oligopeptide sequence one or more times each of them covalently bound to one or more oligopeptides repeat(s) with cyclic topology or other cyclic peptidomemetic. 
         [0017]    In still another embodiment, the oligopeptides sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 that contain two residues of the amino acid cystein are modified to form disulfide bonds thereby changing the secondary and tertiary structure of the oligopeptide as well as epitope formation. 
         [0018]    In one embodiment, modification of any of the sequences identified as SEQ ID No: 1 through SEQ ID NO: 111 by a combination of two or more of the modifications of the invention. 
         [0019]    In another embodiment, the production of natural and/or synthetic peptidomimetics mimicking the three dimensional structure of an oligopeptide sequence according to invention and/or mimicking the three dimensional structure of a modification of such an oligopeptide according to the invention. 
         [0020]    In one embodiment, the preventive or therapeutic use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics to directly and competitively reduce or block infections by the African Swine virus. 
         [0021]    In another embodiment, the preventive or therapeutic use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics to indirectly reduce or block the metabolic action or interaction of African Swine virus by applying them as vaccines by subcutaneous application or in another acceptable way to stimulate a specific immune response which can partially or completely block infections by the African Swine virus. 
         [0022]    In a preferred embodiment, the preventive or therapeutic use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics to directly and competitively reduce or block immune deficiencies. 
         [0023]    In yet another preferred embodiment, the preventive or therapeutic use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics to indirectly reduce or block the metabolic action or interaction of African Swine virus by applying them as vaccines by subcutaneous application or in another acceptable way to stimulate a specific immune response which can partially or completely block immune deficiencies. 
         [0024]    In still yet another preferred embodiment, the use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention to prevent or treat immune deficiencies in any other medically acceptable way. 
         [0025]    In one aspect of the invention, the use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics for the prevention or therapy of infectious diseases. 
         [0026]    In another aspect of the invention, the use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or other peptidomimetics for the prevention or therapy of diseases that may turn out to be caused or related to African Swine virus. 
         [0027]    In yet another aspect of the invention, the preventive and therapeutic use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and/or peptidomimetics according to claim  1  to  10  where the oligopeptides are coupled to haptens to enhance immune response and thereby therapeutic efficacy. 
         [0028]    In still yet another aspect of the invention, the use of one or more of the oligopeptides of claim  1 - 111  and/or modifications thereof identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or other peptidomimetics of the invention for the production of specific antibodies for the diagnosis of a disease involving African Swine virus or the clinical monitoring of the progression or regression of this disease. 
         [0029]    In one preferred embodiment of the invention, the use of one or more of the oligopeptides identified as SEQ ID No: 1 through SEQ ID NO: 111 and/or modifications to the invention and and/or other peptidomimetics for the production of specific antibodies for the diagnosis or the clinical monitoring of the progression or regression of immune deficiencies. 
     
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0030]      FIG. 1  shows the antigenicity scores derived from and according to the Hopp-Woods hydrophylicity algorithm for the protein p54, a 183 amino acid long structural protein of the African Swine virus. Since p54 is involved in the pathogenesis of African Swine fever (2), interrupting this pathogenicity-mediating pathway will lead to a decrease or a complete block of infection by this virus. 
           [0031]    The relative peaks of this algorithm, defined as amino acid sequence regions of either high hydrophilic characteristics or sequence regions of higher hydrophilic characteristics in relation to adjacent amino acid sequences or in comparison to hydrophobic regions of the protein, represent the likely candidate sequence regions (oligopeptides) serving as epitopes (antigens) for antibody formation. Moreover these defined oligopeptide sequences represent the likely region by which a protein interacts with other proteins and/or biological compounds in an organism, including those interactions that mediate infection or other forms of pathogenicity. 
           [0032]    Producing synthetic oligopeptides, corresponding to these algorithm maxima allows the development of preventive and therapeutic agents to control African Swine fever infections. The relative peaks of the Hopp-Woods algorithm for the p54 protein of the African Swine virus selected for this patent application are marked by arrows. The synthetic oligopeptides for the other African Swine fever proteins specified in this disclosure and the claims are selected in an analogous way. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0033]    The African Swine virus is a particular virus the pathogenicity of which is largely determined by targeting the immune system of the host and disabling it. 
         [0034]    Despite the DNA sequence of African Swine virus having been determined (3), there is currently no effective vaccine available to control African Swine fever as documented in the United Nations Food and Agricultural Organization&#39;s field handbook on this disease (4) 
         [0035]    The present invention describes the identification and production of preventive and therapeutic agents, which—among others—can be used as vaccines against African Swine fever with the following specific steps being taken:
       1. The identification of structural proteins and/or pathogenicity-mediating proteins and/or any other protein from the African Swine virus.   2. The analysis of the amino acid sequence of these proteins using specific algorithms allowing the determination of relative hydrophilic and/or polarity and/or charge and/or surface probability peaks and/or any other method allowing the determination of potential epitopes within these African Swine fever virus proteins.   3. The production of synthetic oligopeptides analogous to the epitope forming oligopeptides identified within the amino acid sequence of the African Swine fever virus proteins.   4. The modification of these synthetic oligopeptides to allow or improve antigencity and the formation of antibodies and/or to block pathogenicity of the African Swine fever virus in any other way by
           a. adding one or several predetermined amino acids to the selected oligopeptide sequence;   b. subtracting one or several predetermined amino acids to the selected oligopeptide sequence;   c. replacing one or several predetermined amino acids within the selected oligopeptide sequence;   d. changing the linear topology of the selected oligopeptide to a cyclic topology;   e. forming a linear chain of covalently bound repeats of the selected oligopeptide sequence;   f. forming a cyclic chain of covalently bound repeats of the selected oligopeptide sequence;   g. coupling an originally selected and/or modified oligopeptide to one or more haptens;   h. to improve antigencity and enhance antibody formation in any other possible way;   i. producing natural and/or synthetic peptidomimetics mimicking the three dimensional srtructure of the natural or modified oligopeptide.   
           5. To conduct in vitro and in vivo tests with the selected oligopeptides and/or peptidomimetics in order to establish their efficacy and efficiency as a therapeutic or diagnostic agents.   6. To identify those originally selected and/or modified synthetic oligopeptides and/or peptidomimetics for therapeutic or diagnostic use that
           a. display maximum and/or optimum ability to form antibodies against the African Swine virus as potential therapeutic vaccines;   b. display maximum and/or optimum competitive inhibition of pathogenicity mediating pathways of the African Swine virus as potential therapeutic agents used for—but not limited to—acute therapeutic treatment of African Swine fever;   c. display maximum and/or optimum antigenicity to raise antibodies for the development of tests to diagnose African Swine fever.   
           7. To use those originally selected and/or modified synthetic oligopeptides and/or peptidomimetics as therapeutic vaccines that display maximum and/or optimum ability to form antibodies against the African Swine virus.   8. To use those originally selected and/or modified synthetic oligopeptides and/or peptidomimetics as therapeutic vaccines that display maximum and/or optimum ability for competitive inhibition of pathogenicity mediating pathways of the African Swine virus as potential therapeutic agents used for—but not limited to—the acute therapeutic treatment of African Swine fever.   9. To use those originally selected and/or modified synthetic oligopeptides and/or peptidomimetics that display maximum and/or optimum antigenicity to be used in the development of diagnostic tests or screening procedures for the African Swine virus.       
 
         [0057]    The current invention also describes the application of the current invention for the diagnosis and treatment of immune deficiency conditions in mammals. 
         [0058]    The following are the characteristics of the African Swine Virus:
       1. it targets the immune system of the host   2. it has the following morphological features, in particular it structurally and functionally impairs the lymph nodes and other integral parts of the immune system;   3. its hematological changes includes a significant decrease of CD4 and T-cell counts;   4. both viruses share similar clinical findings, namely lymph node swelling, increased susceptibility to infections, and others;   5. it has both an acute and chronic form of infectious states;   6. it is known to display a high frequency of alteration of their genetic sequence in order to escape the host defense system;   7. it is endemic in sub-Saharan Africa and few other regions.       
 
         [0066]    While the African Swine virus has been primarily detected in pigs and certain other animals, antibodies against the African Swine virus have also been found in humans (5). The fact that there was no description of any finding of the African Swine virus in humans may thus be attributable to oversight or a lack of understanding for the significance of African Swine fever virus for the pathogenicity of immune deficiencies in humans. 
         [0067]    Thus, the inventions described in this patent application can have far reaching implications not only for the control of African Swine fever but also for the control of other immunodeficiency diseases. 
         [0068]    The main structural and/or pathogenicity mediating proteins of the African Swine virus are the following: 
         [0000]    
       
         
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
               
               
             
           
               
                 (SEQ ID NO: 1) 
                   
               
             
          
           
               
                 Ser-Arg-Pro-Pro-Leu-Ser-Ser-Glu-Ala-Asn-Leu-Tyr- 
                   
               
               
                 Ala-Lys-Leu-Gln-Asp-His-Ile-Gln-Arg-Gln-Thr-Arg- 
               
               
                 Pro-Phe-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 2) 
                   
               
             
          
           
               
                 Gly-Asp-Lys-Asn-Pro-Val-Gln-His-Ile-Lys-Asp-Tyr- 
                   
               
               
                 His-Ile-Asp-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 3) 
                   
               
             
          
           
               
                 Ser-Lys-Ala-Lys-Leu-Arg-Val-Ile-Glu-Gly-Ile-Ile- 
                   
               
               
                 Arg-Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 4) 
                   
               
             
          
           
               
                 Phe-Lys-Val-Asp-Thr-Lys-Gln-Pro-Ile-Glu-Asp-Ile- 
                   
               
               
                 Leu-Lys-Asp-Ile-Lys-Lys-Gln-Leu-Pro-Asp-Pro-Arg- 
               
               
                 Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 5) 
                   
               
             
          
           
               
                 Ala-Glu-Lys-Gln-Glu-Thr-Val-Cys-Lys-Met-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 6) 
                   
               
             
          
           
               
                 Gln-Glu-Phe-Ile-Asp-Leu-Gly-Gln-Asp-Lys-Leu-Ile- 
                   
               
               
                 Asp-Thr-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 7) 
                   
               
             
          
           
               
                 Ala-Glu-Lys-Gln-Glu-Thr-Val-Cys-Lys-Met-Ile-Ala- 
                   
               
               
                 Asp-Ala-Ile-Asn-Gln-Glu-Phe-Ile-Asp-Leu-Gly-Gln- 
               
               
                 Asp-Lys-Leu-Ile-Asp-Thr-Thr-Asp-Gly-Ala-Ala-Ser- 
               
               
                 Ile-Cys-Arg-Gln-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 8) 
                   
               
             
          
           
               
                 Leu-Arg-Ala-Glu-Tyr-Leu-Asp-Val-His-Gly-Ser-Ile- 
                   
               
               
                 Glu-Asn-Thr-Leu-Glu-Asn-Ile-Lys-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 9) 
                   
               
             
          
           
               
                 Asn-Asp-Ala-Ile-Lys-Gln-Leu-His-Glu-Arg-Met-Val-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 10) 
                   
               
             
          
           
               
                 Thr-Glu-Val-Thr-Lys-Ala-Ala-Pro-Asn-Glu-Glu-Val-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 11) 
                   
               
             
          
           
               
                 Ile-Glu-Ala-Val-Tyr-Arg-Arg-Leu-Leu-Asn-Glu-Gln- 
                   
               
               
                 Asn-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 12) 
                   
               
             
          
           
               
                 Thr-Gln-Lys-Glu-Leu-Asp-Lys-Leu-Gln-Thr-Asp-Glu- 
                   
               
               
                 Val-Asp-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 13) 
                   
               
             
          
           
               
                 Leu-Cys-Asn-Leu-Gly-Ile-Ala-Ala-Ser-Val-Ala-Asn- 
                   
               
               
                 Lys-Ile-Asn-Lys-Ala-Leu-Gln-Lys-Val-Gly-Leu-Lys- 
               
               
                 Val-Glu-Gln-Tyr-Leu-Gln-Ser-Lys-Asn-Trp-Ala-Glu- 
               
               
                 Phe-Asp-Lys-Glu-Leu-Asp-Leu-Lys-Arg-Phe-Ser-Gly- 
               
               
                 Leu-Val-Ser-Ala-Glu-Asn-Ile-Ala-Glu-Phe-Glu-Lys- 
               
               
                 Ala-Val-Asn-Leu-Leu-Arg-Gln-Thr-Phe-Asn-Glu-Arg- 
               
               
                 His-Lys-Ile-Leu-Glu-Asn-Ser-Cys-Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 14) 
                   
               
             
          
           
               
                 Asn-Lys-Ile-Asn-Lys-Ala-Leu-Gln-Lys-Val-Gly-Leu- 
                   
               
               
                 Lys-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 15) 
                   
               
             
          
           
               
                 Ser-Lys-Asn-Trp-Ala-Glu-Phe-Asp-Lys-Glu-Leu-Asp- 
                   
               
               
                 Leu-Lys-Arg-Phe-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 16) 
                   
               
             
          
           
               
                 Ala-Glu-Asn-Ile-Ala-Glu-Phe-Glu-Lys-Ala-Val-Asn- 
                   
               
               
                 Leu-Leu-Arg-Gln-Thr-Phe-Asn-Glu-Arg-His-Lys-Ile- 
               
               
                 Leu-Glu-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 17) 
                   
               
             
          
           
               
                 Ala-Lys-Lys-Gly-Gly-Asp-Glu-Glu-Lys-Thr-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 18) 
                   
               
             
          
           
               
                 Pro-Leu-Asp-Arg-Arg-Ile-Glu-Ala-Gln-Arg-Leu-Asp- 
                   
               
               
                 Arg-Lys-His-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 19) 
                   
               
             
          
           
               
                 Ala-Lys-Lys-Gly-Gly-Asp-Glu-Glu-Lys-Thr-Pro-Leu- 
                   
               
               
                 Asp-Arg-Arg-Ile-Glu-Ala-Gln-Arg-Leu-Asp-Arg-Lys- 
               
               
                 His-Glu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 20) 
                   
               
             
          
           
               
                 Asn-Asp-Phe-Leu-Glu-Asn-Val-Lys-Lys-Ile-Gly-Ile- 
                   
               
               
                 Lys-Leu-Val-Lys-Glu-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 21) 
                   
               
             
          
           
               
                 Thr-Arg-Leu-Arg-Asp-Ala-Leu-Ser-Arg-Ile-Asn-Asp- 
                   
               
               
                 Met-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 22) 
                   
               
             
          
           
               
                 Ala-Arg-Glu-Glu-Arg-Glu-Thr-Phe-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 23) 
                   
               
             
          
           
               
                 Val-Lys-Asn-Val-Leu-Glu-Glu-Gln-Ser-Lys-Ile-Asp- 
                   
               
               
                 Pro-Asn-Phe-Lys-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 24) 
                   
               
             
          
           
               
                 Tyr-Asp-Ser-Cys-Ser-Arg-Leu-Leu-Gln-Ile-Ile-Asp- 
                   
               
               
                 Phe-Tyr-Thr-Asp-Ile-Val-Gln-Lys-Lys-Tyr-Gly-Gly- 
               
               
                 Gly-Glu-Asp-Cys-Glu-Cys-Thr-Arg-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 25) 
                   
               
             
          
           
               
                 Tyr-Asp-Ser-Cys-Ser-Arg-Leu-Leu-Gln-Ile-Ile-Asp- 
                   
               
               
                 Phe-Tyr-Thr-Asp-Ile-Val-Gln-Lys-Lys-Tyr-Gly-Gly- 
               
               
                 Gly-Glu-Asp-Cys-Glu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 26) 
                   
               
             
          
           
               
                 Val-Gln-Lys-Lys-Tyr-Gly-Gly-Gly-Glu-Asp-Cys-Glu- 
                   
               
               
                 Cys-Thr-Arg-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 27) 
                   
               
             
          
           
               
                 Val-Glu-Glu-Leu-Gly-Leu-Ser-Lys-Ala-Ala-Arg-Ser- 
                   
               
               
                 Gln-Val-Asp-Leu-Asn-Gln-Ala-Ile-Asn-Thr-Phe-Met- 
               
               
                 Tyr-Tyr-Tyr-Tyr-Val-Ala-Gln-Ile-Tyr-Ser-Asn-Leu- 
               
               
                 Thr-His-Asn-Lys-Gln-Glu-Phe-Gln-Ser-Tyr-Glu-Glu- 
               
               
                 Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 28) 
                   
               
             
          
           
               
                 Thr-His-Asn-Lys-Gln-Glu-Phe-Gln-Ser-Tyr-Glu-Glu- 
                   
               
               
                 Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 29) 
                   
               
             
          
           
               
                 Met-Gln-Leu-Asp-Thr-Glu-Lys-Asn-Ala-Arg-Ile-Asn- 
                   
               
               
                 Ser-Pro-Ala-Val-Asp-Leu-Ala-Arg-Gly-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 30) 
                   
               
             
          
           
               
                 Ala-Gln-Glu-Ala-Asp-Trp-Lys-Ala-Ala-Val-Ser-Ala- 
                   
               
               
                 Ile-Glu-Leu-Glu-Tyr-Asp-Val-Lys-Arg-Arg-Phe-Tyr- 
               
               
                 Arg-Ala-Leu-Glu-Gly-Leu-Asp-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 31) 
                   
               
             
          
           
               
                 Leu-Lys-Asn-Ile-Thr-Lys-Thr-Phe-Val-Asn-Asn-Ile- 
                   
               
               
                 Asp-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 32) 
                   
               
             
          
           
               
                 Leu-Asp-Gly-Val-Arg-Ile-Ile-Gly-Arg-Trp-Phe-Thr- 
                   
               
               
                 Glu-Ala-Thr-Gly-Asp-Thr-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 33) 
                   
               
             
          
           
               
                 Ala-Glu-Ile-Gln-Gln-Gly-Arg-Ser-Val-Gly-Thr-Leu- 
                   
               
               
                 Arg-Pro-Val-Arg-Ala-Ser-Gln-Ala-Lys-Asn-Ile-Arg- 
               
               
                 Asp-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 34) 
                   
               
             
          
           
               
                 Ala-Arg-Ile-Gly-Asp-Met-Leu-Gly-Gly-Glu-Glu-Leu- 
                   
               
               
                 Arg-Gln-Met-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 35) 
                   
               
             
          
           
               
                 Leu-Lys-Asn-Leu-Asn-Gln-Ser-Glu-Ile-Gly-Gly-Gln- 
                   
               
               
                 Arg-Val-Ala-Leu-Ala-Arg-Thr-Pro-Glu-Glu-Ala-Ala- 
               
               
                 Gln-Arg-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 36) 
                   
               
             
          
           
               
                 Asn-Asp-Ala-Leu-Ser-Thr-Arg-Trp-Glu-Thr-Glu-Asp- 
                   
               
               
                 Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 37) 
                   
               
             
          
           
               
                 Tyr-Asp-Met-Phe-Glu-Arg-Pro-Glu-Pro-Val-Tyr-Lys- 
                   
               
               
                 Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 38) 
                   
               
             
          
           
               
                 Ala-Asp-Glu-Leu-Glu-Pro-Glu-Val-Ile-Pro-Glu-Ala- 
                   
               
               
                 Ala-Glu-Leu-Tyr-Phe-Arg-Leu-Pro-Arg-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 39) 
                   
               
             
          
           
               
                 Phe-Arg-Leu-Pro-Arg-Leu-Ala-Glu-Phe-Tyr-Gln-Lys- 
                   
               
               
                 Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 40) 
                   
               
             
          
           
               
                 Met-Arg-Pro-Ile-Glu-Leu-Ile-Asn-Ile-Gly-Asp-Tyr- 
                   
               
               
                 Ser-Glu-Thr-Glu-Ile-Arg-Gln-Leu-Ile-Lys-Glu-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 41) 
                   
               
             
          
           
               
                 Leu-Glu-Tyr-Gly-Glu-Gln-Glu-Ala-Thr-Lys-Lys-Ala- 
                   
               
               
                 Leu-Ile-His-Phe-Val-Asn-Glu-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 42) 
                   
               
             
          
           
               
                 Asn-Arg-Arg-Phe-Gly-Val-Ile-Thr-Arg-Thr-Glu-Trp- 
                   
               
               
                 Glu-Lys-Phe-Gln-Arg-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 43) 
                   
               
             
          
           
               
                 Gln-Arg-Ile-Val-Gln-Glu-Ala-Arg-Thr-Met-Asn-Asp- 
                   
               
               
                 Phe-Gly-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 44) 
                   
               
             
          
           
               
                 Ser-Gln-Trp-Asp-Leu-Val-Gln-Lys-Phe-Arg-Lys-Gln- 
                   
               
               
                 Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 45) 
                   
               
             
          
           
               
                 Gln-Lys-Phe-Arg-Lys-Gln-Leu-Ser-Glu-Met-Phe-Glu- 
                   
               
               
                 Asp-Pro-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 46) 
                   
               
             
          
           
               
                 Gln-Gln-Glu-Leu-Gly-Lys-Val-Ser-Tyr-Gln-Glu-Leu- 
                   
               
               
                 Ile-Arg-Gln-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 47) 
                   
               
             
          
           
               
                 Ile-Asn-Glu-Leu-Lys-Lys-Glu-His-Thr-Asp-Lys-Ile- 
                   
               
               
                 Gln-Ile-Val-Ser-Lys-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 48) 
                   
               
             
          
           
               
                 Leu-Lys-Lys-Glu-His-Thr-Asp-Lys-Ile-Gln-Ile-Val- 
                   
               
               
                 Ser-Lys-Leu-Ile-Gln-Gly-Ser-Glu-Ser-Leu-Ala-Asp- 
               
               
                 Thr-Asp-Val-Asn-Lys-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 49) 
                   
               
             
          
           
               
                 Phe-Arg-Asn-Asn-Ile-Lys-Gly-Leu-Asp-Leu-Asp-Thr- 
                   
               
               
                 Ile-Gln-Lys-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 50) 
                   
               
             
          
           
               
                 Ile-Glu-Trp-Leu-Arg-Glu-Thr-Gln-Ala-Ala-Asn-Val- 
                   
               
               
                 Asn-Arg-Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 51) 
                   
               
             
          
           
               
                 Ile-Asp-Trp-Leu-Gly-Arg-Lys-His-Gly-Ala-Ile-Ser- 
                   
               
               
                 Glu-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 52) 
                   
               
             
          
           
               
                 Ile-Arg-Asn-Pro-Gly-Leu-Val-Val-Lys-Glu-Asn-Asp- 
                   
               
               
                 Val-Arg-Leu-Ser-Arg-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 53) 
                   
               
             
          
           
               
                 Ala-Glu-Gln-Glu-Leu-Ala-Ala-Arg-Tyr-Leu-Val-Asp- 
                   
               
               
                 Asn-Gln-Arg-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 54) 
                   
               
             
          
           
               
                 Phe-Asn-Lys-Met-Val-Gln-Val-Arg-Phe-Pro-Glu-Thr-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 55) 
                   
               
             
          
           
               
                 Ile-Asp-Ser-Leu-Met-Ala-Asp-Thr-Lys-Tyr-Phe-Leu- 
                   
               
               
                 Asn-Leu-Leu-Arg-Pro-His-Ile-Asp-Lys-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 56) 
                   
               
             
          
           
               
                 Leu-Glu-Glu-His-Leu-Ile-Asp-Lys-Leu-Ile-Lys-Pro- 
                   
               
               
                 Pro-Thr-Asp-Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 57) 
                   
               
             
          
           
               
                 Leu-Gln-Leu-Arg-Gly-Gly-Val-Gln-Arg-Arg-Asp-Ala-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 58) 
                   
               
             
          
           
               
                 Ser-Glu-Arg-Phe-Glu-Gln-Tyr-Gly-Arg-Val-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 59) 
                   
               
             
          
           
               
                 Leu-Gln-Leu-Arg-Gly-Gly-Val-Gln-Arg-Arg-Asp-Ala- 
                   
               
               
                 Ala-Asn-Ile-Gln-Ile-Asn-Asn-Asn-Pro-Gln-Pro-Ser- 
               
               
                 Glu-Arg-Phe-Glu-Gln-Tyr-Gly-Arg-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 60) 
                   
               
             
          
           
               
                 Ile-Arg-Thr-Asn-Asn-Ala-Gln-Glu-Glu-Asn-Thr-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 61) 
                   
               
             
          
           
               
                 Leu-Arg-Arg-Tyr-Arg-Leu-Tyr-Gly-Ser-Asp-Tyr-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 62) 
                   
               
             
          
           
               
                 Ala-Arg-Phe-Tyr-Asp-Ala-Pro-Ser-Gly-Lys-Ile-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 63) 
                   
               
             
          
           
               
                 Met-Glu-Leu-Gly-Tyr-Thr-His-Pro-Asp-Leu-Ala-Arg- 
                   
               
               
                 Asp-Asn-Ile-Ala-Phe-Gly-His-Arg-Gly-Asp-Pro-Thr- 
               
               
                 Glu-Gln-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 64) 
                   
               
             
          
           
               
                 Leu-Gln-Arg-Leu-Ile-Lys-Asp-Thr-Asn-Arg-Gln-Gly-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 65) 
                   
               
             
          
           
               
                 Thr-Glu-Ile-Pro-Ile-Tyr-Leu-Lys-Glu-Asn-Tyr-Arg- 
                   
               
               
                 Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 66) 
                   
               
             
          
           
               
                 Leu-Gln-Arg-Leu-Ile-Lys-Asp-Thr-Asn-Arg-Gln-Gly- 
                   
               
               
                 Leu-Ser-Gln-His-Leu-Ile-Ser-Thr-Leu-Thr-Glu-Ile- 
               
               
                 Pro-Ile-Tyr-Leu-Lys-Glu-Asn-Tyr-Arg-Ala-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 67) 
                   
               
             
          
           
               
                 Ser-Asp-Val-Val-Arg-Lys-Arg-Leu-Val-Ala-Val-Ile- 
                   
               
               
                 Asp-Gly-Ile-Ile-Arg-Gly-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 68) 
                   
               
             
          
           
               
                 Tyr-Leu-Glu-Thr-Glu-Glu-His-Phe-Ile-Gln-Asn-Tyr- 
                   
               
               
                 Met-Ser-Arg-Tyr-Asn-Lys-Glu-Pro-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 69) 
                   
               
             
          
           
               
                 Tyr-Leu-Arg-Asp-Leu-Arg-Ile-Glu-Asn-Asn-Glu-Val- 
                   
               
               
                 Tyr-Asp-Pro-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 70) 
                   
               
             
          
           
               
                 Leu-Glu-Ser-Gly-Ser-Pro-Glu-Phe-Lys-Leu-Leu-Tyr- 
                   
               
               
                 Gly-Thr-Arg-Lys-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 71) 
                   
               
             
          
           
               
                 Met-Lys-Asn-Tyr-Asn-Glu-Thr-Val-Val-Ala-Arg-Glu- 
                   
               
               
                 Gln-Ile-Thr-Pro-Thr-Arg-Phe-Glu-His-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 72) 
                   
               
             
          
           
               
                 Ile-Ser-Glu-Asn-Arg-Asp-Asp-Lys-Pro-Ile-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 73) 
                   
               
             
          
           
               
                 Leu-Arg-Lys-Thr-Leu-Gln-Asp-Val-Ile-Ser-Phe-Val- 
                   
               
               
                 Glu-Ser-Ser-Tyr-Gln-Glu-Glu-Gln-Ile-Asn-His-Ile- 
               
               
                 His-Lys-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 74) 
                   
               
             
          
           
               
                 Pro-Lys-Gly-Gln-Thr-Arg-Thr-Leu-Gly-Ser-Asn-Arg- 
                   
               
               
                 Glu-Arg-Glu-Arg-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 75) 
                   
               
             
          
           
               
                 Tyr-Asp-Tyr-Ser-Phe-Glu-Glu-Ile-Ala-Cys-Leu-Met- 
                   
               
               
                 Tyr-Gly-Ile-Ser-Ala-Glu-Lys-Val-Arg-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 76) 
                   
               
             
          
           
               
                 Pro-Asp-Ile-Ala-Glu-Val-Leu-Asn-Ile-Pro-Asn-Arg- 
                   
               
               
                 Pro-Pro-Met-Asn-Thr-Arg-Glu-Phe-Met-Leu-Lys-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 77) 
                   
               
             
          
           
               
                 Met-Ser-Arg-Ile-Phe-Arg-Gly-Asp-Asn-Ala-Leu-Asn- 
                   
               
               
                 Met-Gly-Arg-Pro-Lys-Phe-Leu-Ser-Asp-Gln-Ile-Phe- 
               
               
                 Asn-Lys-Val-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 78) 
                   
               
             
          
           
               
                 Ile-Gln-Arg-Gly-Arg-Glu-Gln-Trp-Gly-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 79) 
                   
               
             
          
           
               
                 Glu-Tyr-Ile-Asn-Gln-Ala-Leu-His-Glu-Leu-Val-Arg- 
                   
               
               
                 Thr-Ile-Arg-Ile-Pro-Gln-Lys-Leu-Arg-Val-Leu-Arg- 
               
               
                 Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 80) 
                   
               
             
          
           
               
                 Ile-Arg-Glu-Gln-Leu-Val-Ser-Met-Arg-Arg-Glu-Val- 
                   
               
               
                 Glu-Asn-Met-Ile-Gln-Thr-Pro-Glu-Ile-Gln-Asn-Asn- 
               
               
                 Pro-Thr-Pro-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 81) 
                   
               
             
          
           
               
                 Thr-Gln-Gln-Tyr-Arg-Ala-Arg-Val-Asp-Thr-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 82) 
                   
               
             
          
           
               
                 His-Pro-Arg-Gln-Ile-Leu-Gln-Thr-Asp-Asp-Glu-Ala-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 83) 
                   
               
             
          
           
               
                 Thr-Asp-Leu-Ala-Asn-Asp-Leu-Arg-Thr-Phe-Leu-Glu- 
                   
               
               
                 Thr-Leu-Glu-Arg-Tyr-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 84) 
                   
               
             
          
           
               
                 Gly-Arg-Val-Ala-Arg-Ala-Pro-Val-Arg-Met-Ala-Pro- 
                   
               
               
                 Arg-Asp-Met-Arg-His-Pro-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 85) 
                   
               
             
          
           
               
                 Thr-Asp-Leu-Ala-Asn-Asp-Leu-Arg-Thr-Phe-Leu-Glu- 
                   
               
               
                 Thr-Leu-Glu-Arg-Tyr-Val-Phe-Asn-Val-Pro-Arg-Trp- 
               
               
                 Leu-Gly-Pro-Ser-Thr-Gly-Arg-Val-Ala-Arg-Ala-Pro- 
               
               
                 Val-Arg-Met-Ala-Pro-Arg-Asp-Met-Arg-His-Pro-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 86) 
                   
               
             
          
           
               
                 Thr-Glu-Gln-Asn-Arg-Glu-Glu-Gly-Pro-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 87) 
                   
               
             
          
           
               
                 Thr-Glu-Gln-Asn-Arg-Glu-Glu-Gly-Pro-Trp-Ser-Ile- 
                   
               
               
                 Val-Lys-Gln-Val-Gly-Val-Gly-Ile-Gln-Lys-Pro-Thr- 
               
               
                 Leu-Val-Gln-Ile-Gly-Lys-Asp-Arg-Phe-Asp-Thr-Arg- 
               
               
                 Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 88) 
                   
               
             
          
           
               
                 Gly-Lys-Asp-Arg-Phe-Asp-Thr-Arg-Leu-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 89) 
                   
               
             
          
           
               
                 Ile-Gln-Arg-Leu-Leu-Arg-Leu-Arg-Leu-Asn-Leu-Glu- 
                   
               
               
                 Leu-Ser-Gln-Phe-Arg-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 90) 
                   
               
             
          
           
               
                 Val-Gln-Ile-Gly-Lys-Asp-Arg-Phe-Asp-Thr-Arg-Leu- 
                   
               
               
                 Ile-Arg-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 91) 
                   
               
             
          
           
               
                 Ile-Gln-Arg-Leu-Leu-Arg-Leu-Arg-Leu-Asn-Leu-Glu- 
                   
               
               
                 Leu-Ser-Gln-Phe-Arg-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 92) 
                   
               
             
          
           
               
                 Ser-Glu-Thr-Phe-Ser-Asp-Lys-Gln-Tyr-Asp-Ser-Asp- 
                   
               
               
                 Ile-Arg-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 93) 
                   
               
             
          
           
               
                 Trp-Glu-Ser-Asp-Leu-Pro-Arg-His-Asn-Arg-Tyr-Ser- 
                   
               
               
                 Asp-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 94) 
                   
               
             
          
           
               
                 Asn-Glu-Tyr-Thr-Asn-Ser-Pro-Glu-Lys-Ala-Glu-Lys- 
                   
               
               
                 Gly-Leu-Gln-Leu-Ser-Asp-Leu-Arg-Asn-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 95) 
                   
               
             
          
           
               
                 Gln-His-Lys-Asn-Ile-Gly-Tyr-Gly-Asp-Ala-Gln-Asp- 
                   
               
               
                 Leu-Glu-Pro-Tyr-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 96) 
                   
               
             
          
           
               
                 Gly-Asp-Ala-Gln-Asp-Leu-Glu-Pro-Tyr-Ser-Ser-Ile- 
                   
               
               
                 Pro-Lys-Asn-Lys-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 97) 
                   
               
             
          
           
               
                 Thr-Glu-Asn-Leu-Ile-Arg-Arg-Asn-Val-Val-Arg-Thr- 
                   
               
               
                 Glu-Lys-Lys-Thr-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 98) 
                   
               
             
          
           
               
                 Thr-Arg-Phe-Ser-Glu-His-Thr-Lys-Phe-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 99) 
                   
               
             
          
           
               
                 Tyr-Glu-Asp-Ile-Pro-Lys-Leu-Lys-Thr-Lys-Gly-Thr- 
                   
               
               
                 Ile-Lys-His-Glu-Gln-His-Leu-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 100) 
                   
               
             
          
           
               
                 Val-Glu-Lys-Gly-Ile-Ala-Gly-Arg-Gly-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 101) 
                   
               
             
          
           
               
                 Val-Lys-Pro-Asn-Ile-Glu-Gln-Glu-Leu-Ile-Lys-Ser-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 102) 
                   
               
             
          
           
               
                 Val-Glu-Lys-Gly-Ile-Ala-Gly-Arg-Gly-Ile-Pro-Leu- 
                   
               
               
                 Gly-Asn-Pro-His-Val-Lys-Pro-Asn-Ile-Glu-Gln-Glu- 
               
               
                 Leu-Ile-Lys-Ser-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 103) 
                   
               
             
          
           
               
                 Pro-Lys-Asp-Ser-Gln-His-Gly-Arg-Glu-Tyr-Gln-Glu- 
                   
               
               
                 Phe-Ser-Ala-Asn-Arg-His; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 104) 
                   
               
             
          
           
               
                 Ile-Lys-Pro-Gln-Ile-Leu-Glu-Asp-Ile-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 105) 
                   
               
             
          
           
               
                 Ser-Lys-Arg-Asn-Ser-Gly-Gln-Ala-Glu-Tyr-Phe-Asp- 
                   
               
               
                 Thr-Ser-Lys-Gln-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 106) 
                   
               
             
          
           
               
                 Gly-Asp-Ser-Lys-Leu-Asp-Ser-Thr-Phe-Pro-Lys-Asp-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 107) 
                   
               
             
          
           
               
                 Ala-Glu-Lys-Asp-His-Ser-Leu-Arg-Gly-Asp-Asn-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 108) 
                   
               
             
          
           
               
                 Ser-Ala-Glu-Lys-Asp-His-Ser-Leu-Arg-Gly-Asp-Asn- 
                   
               
               
                 Ser-Ala-Cys-Cys-Ile-Ser-Asn-Tyr-Ile-Pro-Lys-Tyr- 
               
               
                 Thr-Gly-Gly-Ile-Gly-Asp-Ser-Lys-Leu-Asp-Ser-Thr- 
               
               
                 Phe-Pro-Lys-Asp-Phe-Asn-Ala-Ser-Ser-Val-Pro-Leu- 
               
               
                 Thr-Ser-Ala-Glu-Lys-Asp-His-Ser-Leu-Arg-Gly-Asp- 
               
               
                 Asn-Ser-Ala-Cys-Cys-Ile-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 109) 
                   
               
             
          
           
               
                 Gly-Asp-Ser-Lys-Leu-Asp-Ser-Thr-Phe-Pro-Lys-Asp- 
                   
               
               
                 Phe-; 
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 110) 
                   
               
             
          
           
               
                 Ala-Glu-Lys-Asp-His-Ser-Leu-Arg-Gly-Asp-Asn-; 
                   
               
               
                   
               
             
          
           
               
                 (SEQ ID NO: 111) 
                   
               
             
          
           
               
                 Gly-Asp-Ser-Lys-Leu-Asp-Ser-Thr-Phe-Pro-Lys-Asp- 
                   
               
               
                 Phe-Asn-Ala-Ser-Ser-Val-Pro-Leu-Thr-Ser-Ala-Glu- 
               
               
                 Lys-Asp-His-Ser-Leu-Arg-Gly-Asp-Asn-. 
               
             
          
         
       
     
       REFERENCES CITED  
       [0000]    
       
         1. Duncan R A et al. Idiopathic CD4+ T-lymphocytopenia—four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993; 328(6): 393-8. 
         2. Rodriguez F et al. Characterization and molecular basis of heterogeneity of the African Swine Fever virus envelope protein p54. J Virol 1994; 68 (11): 7244-7252. 
         3. Yanez R J et al. Analysis of the complete nucleotide sequence of African Swine Fever virus. Virology 1995; 208: 249-278. 
         4. Recognizing African Swine Fever, A Field Manual, UN Food and Agricultural Organization, ISBN 92-5-104471-6 
         5. Hess W R. African Swine Fever: A Reassessment. Advances in Veterinary Science and Comparative Medicine Vol. 25. Cornelius C E, Simpson C F eds. Academic Press, New York, 1981:39-69.