HIV PROTEINS AND PEPTIDES USEFUL IN THE DIAGNOSIS, PROPHYLAXIS OR THERAPY OF AIDS

Abstract: The subject invention concerns the identification of a portion of the HIV envelope protein called the principal neutralizing domain. Polypeptides comprising this domain have the capability of raising, and/or binding with, neutralizing antibodies. The invention further concerns novel HIV polypeptides which can be used in the diagnosis, prophylaxis, or therapy of AIDS. These polypeptides can be prepared by known chemical synthetic procedures, or by recombinant DNA means. The polypeptides pertain to the gp 120 subunit, amino acids 298-320, including the sequence .......gly-pro-gly...... and variants thereof. Multiepitope polypeptides comprising analogues of this peptide epitope from different HIV variants are referred to.

Description: DESCRIPTION HIV PROTEINS AND PEPTTDES USEFUL IN THE DIAGNOSIS. PROPHYLAXIS OR THERAPY OF AIDS Cross-Reference to a Related Application This is a continuation-in-part of our co-pending application Serial No. 359,543, filed on Jun 1, 1989, which is a continuation-in-part of our co-pending application Serial No. 252,949, filed o October 3, 1988, which is a continuation-in-part of our co-pending application Serial No. 090,080, file on August 27, 1987. Background of the Invention Human immunodeficiency virus (HIV), human T-cell lymphotropic virus HI (HTLV-III) lymphadenopathy-associated virus (LAV), or AIDS-associated retrovirus (ARV) has been identifie as the cause of acquired immune deficiency syndrome (AIDS) (Popovic, M., M.G. Sarngadharan, Read, and R.C. Gallo [1984] Science 224:497-500). The virus displays tropism for the OKT4 lymphocyte subset (Klatzmann, D., F. Barre-Sinoussi, M.T. Nugeyre, C Dauget, E. Vilmer, C. Griscelli F. Brun-Vezinet, C Rouzioux, J.D. Gluck an, J.C. Chermann, and L. Montagnier [1984] Scienc 225:59-63). Antibodies against HIV proteins in the sera of most AIDS and AIDS related comple (ARC) patients, and in asymptomatic people infected with the virus (Sarngadharan, M.G., M. Popovi L. Bruch, J. Schupbach, and R.C. Gallo [1984] Science 224:506-508) have made possible th development of immunologically based tests that detect antibodies to these antigens. These tests ar used to limit the spread of HIV through blood transfusion by identifying blood samples of peopl infected with the virus. Diagnostic tests currently available commercially use the proteins o inactivated virus and antigens. In addition to allowing new approaches for diagnosis, recombinant DNA holds great promis for the development of vaccines against both bacteria and viruses (Wilson, T. [1984] Bio/Technolog 2:29-39). The most widely employed organisms to express recombinant vaccines have been E. coli, cerevisiae and cultured mammalian cells. For example, subunit vaccines against foot and mout disease (Kleid, D.G., D. Yansura, B. Small, D. Dowbenko, D.M. Moore, M.J. Brubman, P. McKercher, D.O. Morgan, B.H. Robertson, and H.L. Bachrach [1981] Science 214:1125-1129) an malaria (Young, J.F., W.T. Hockmeyer, M. Gross, W. Ripley-Ballou, R.A. Wirtz, J.H. Trosper, R. Beaudoin, M.R. Hollingdale, L.M. Miller, CL. Diggs, and M. Rosenberg [1985] Science 228:958-962 have been synthesized in R coli. Other examples are hepatitis B surface antigen produced in yeas (McAleer, W.J., E.B. Buynak, R.Z. Maigetter, D.E. Wamplcr, W.J. Miller, and M.R. Hilleman [1984 Nature 307:178-180) and a herpes vaccine produced in mammalian cells (Berman, P.W., T. Gregor D. Chase, and L.A. Lasky [1984] Science 227:1490-1492). The entire HIV envelope or portions thereof have been used to immunize animals. The ter "protein," "peptide," and "polypeptide" have been used interchangeably in this application to refer chemical compounds having more than one amino acid. The term "compound" as used here refers chemical compounds in general. Thus, "compound" includes proteins, peptides, and polypeptides. Al included under the category of "compound" are fusion compounds where polypeptides are combin with non-polypeptide moieties. As used in the present application, the term "naturally occurring H envelope protein" refers to the proteins gpl60, gpl20, and gp41 only. As used in the pres application, HIV refers to any HIV virus, including HIV-1 and HIV-2. Both the native gpl20 (Robey et al. [1986] Proc. Natl. Acad. Sci. 83:7023-7027; Matthews al. [1986] Proc. Natl. Acad. Sci. 83:9709-9713) and recombinant proteins (Laskey et al. [1986] Scie 233:209-212; Putney et al. [1986] Science 234:1392-1395) elicit antibodies that can neutralize HIV cell culture. However, all of these immunogens elicit antibodies that neutralize only the viral vari from which the subunit was derived. Therefore, a novel vaccine capable of protecting against multi viral variants would be advantageous and unique. HIV is known to undergo amino acid sequence variation, particularly in the envelope ge (Starcich, B.R. [1986] Cell 45:637-648; Hahn, B.H. et al. [1986] Science 232:1548-1553). Over 1 variants have been analyzed by molecular cloning and restriction enzyme recognition analysis, a several of these have been analyzed by nucleotide sequencing. Some of these are the HIV isola known as RF (Popovic, M. et al. [1984] Science 224:497-500), WMJ-1 (Hahn, B.H. et al. [19 Science 232:1548-1553), LAV (Wain-Hobson, S. et al. [1985] Cell 40:9-17), and ARV-2 (Sanch Pescador, R. et al. [1985] Science 227:484-492). One aspect of this invention is defining the porti of HIV that comprises the principal neutralizing domain. The principal neutralizing domain is loca between the cysteine residues at amino acids 296 and 331 of the HIV envelope. The numbering amino acids follows the published sequence of HIV-III B (Ratner, L. et al. [1985] Nature 313:2 284). This domain is known to be hypervariable but retains the type-specific antigenic a immunogenic properties related to virus neutralization. A further aspect of the subject invention is the discovery of highly conserved amino ac within the principal neutralizing domain. Although certain sequences from this region have b published (see, for example, Southwest Foundation for Biological Research, published PCT applicati Publication No. WO 87/02775; Genetic Systems Corporation, Published United Kingdom Applicati No. GB 2196634 A; Stichting Centraal Diergeneeskundig Instiluut, Published EPO Application 0 311 219), the presence of the conserved regions described here have never before been describ Diagnostic kits or therapeutic agents using viral proteins isolated from virus infected cells recombinant proteins would contain epitopes specific to the viral variant from which they w isolated. Reagents containing proteins from multiple variants would have the utility of being m broadly reactive due to containing a greater diversity of epitopes. This would be advantageous in screening of serum from patients or therapeutic treatment of patients. Synthetic peptides can be advantageous as the active ingredient in a vaccine, therapeutic agen or diagnostic reagent due to the ease of manufacture and ability to modify their structure and mod of presentation. Synthetic peptides have been used successfully in vaccination against foot and mouth diseas virus (Bittle et al. [1982] Nature 29830-33); poliovirus (Emini et al. [1983] Nature 305:699); hepatiti B (Gerin et al. [1983] Proc. Natl. Acad. Sci. 80:2365-2369); and influenza (Shapira et al. [1984] Pro Natl. Acad. Sci. 81:2461-2465). There is a real need at this time to develop a vaccine for AIDS. Such a vaccin advantageously, would be effective to immunize a host against the variant AIDS viruses. Brief Summary nf the Invention The subject invention defines the location of the HIV principal neutralizing domain an discloses methods to utilize this segment of the HTV envelope protein for developing diagnosti therapeutic, and prophylactic reagents. More specifically, the HTV principal neutralizing domain located between cysteine residues 296 and 331 of the HTV envelope protein. The location of th domain is shown in Table 1. Although the specific amino acid sequence of the principal neutralizin domain is known to be highly variable between variants, we have found that peptides from this domai are invariably capable of raising, and/or binding with, neutralizing antibodies. This unexpecte discovery provides a basis for designing compositions and strategies for the prevention, diagnosis, an treatment of AIDS. The discovery of the principal neutralizing domain (also known as the "loop") resulted fro extensive research involving a multitude of HTV envelope proteins and peptides from many HI variants. Proteins and peptides capable of raising, and/or binding with, neutralizing antibodies a disclosed here. These novel HIV proteins and peptides, or their equivalents, can be used in t diagnosis, prophylaxis, and/or therapy of AIDS. Further, the peptides can be used as immunogens screening reagents to generate or identify polyclonal and monoclonal antibodies that would be usef in prophylaxis, diagnosis and therapy of HTV infection. A further aspect of the invention is the discovery of highly conserved regions within t principal neutralizing domain. This discovery was quite unexpected because of the known variabili of the amino acids within this segment of the HIV envelope protein. The proteins and peptides of the invention are identified herein by both their amino ac sequences and the DNA encoding them. Thus, they can be prepared by known chemical synthet procedures, or by recombinant DNA means. These peptides, or peptides having the antigenic or immunogenic properties of these peptid can be used, advantageously, in a vaccine, e.g., a cocktail of peptides, to elicit broad neutralizi antibodies in the host. Further, these peptides can be used sequentially, e.g., immunizing initially wi a peptide equivalent to the principal neutralizing domain of an HIV variety followed by immunizati with one or more of the above peptides. Polyclonal or monoclonal antibodies that bind to thes peptides would be advantageous in prophylaxis or therapy against HIV, the causative agent of AID Brief Description of the Drawings Figure 1 shows commonly occurring sequences of the principal neutralizing domain. Figure 2 is a schematic for multi-epitope gene construction. Figure 3 depicts the steps in the construction of a specific multi-epitope gene. Figure 4 shows the sequences of four synthesized single-stranded oligomers for constructio of a multi-epitope gene. Detailed Disclosure of the Invention Described here is a segment of the HIV envelope protein which raises, and/or binds wit neutralizing antibodies. This unique and highly unexpected property has been observed in each HI variant that has been examined. The segment of interest has been named the "principal neutralizi domain." The principal neutralizing domain is bounded by cysteine residues which occur at positio 296 and 331. It should be noted that these same cysteine residues have been described as beginni at 302, rather than 296 (Rusche, J.R. et al. [1988] Proc Natl. Acad. Sci. USA 85(15):3198-3202 Because the cysteine residues are linked through disulfide bonds, the segment between the residu tends to form a loop. Therefore, the principal neutralizing domain is also referred to as the "loop The segment of the protein envelope identified here as the principal neutralizing domain known to be highly variable between HIV variants. Thus it is surprising that, for each variant, th segment is capable of eliciting, and/or binding with, neutralizing antibodies. The principal neutralizing domain identified here is a small segment of the HIV envelo protein. This small segment may be combined with additional amino acids, if desired, for a specif purpose. All such proteins are claimed here except where such proteins constitute a natural occurring HIV envelope protein. As used here, the term "naturally occurring envelope protein" refe only to gpl60, gpl20, and gp41. Listed in Table 1 are sequences of the principal neutralizing domain for some of the varian tested. Table 9 contains a complete list of the principal neutralizing domains. Amino acids may be referred to using either a three-letter or one-letter abbreviation syste The following is a list of the common amino acids and their abbreviations: One-letter svmbol A R N D B C Q E Z G H I L K M F P S T w Y V The following is a list of proteins and peptides which comprise principal neutralizing domai or segments thereof. A. Recombinant Proteins Comprising a Principal Neutralizing Domain 1. HIV 10 Kd fusion protein denoted Sub 1. The amino acid sequence of the HI portion of Sub 1 is shown in Table 2 and the DNA sequence of the HIV portion Sub 1 in Table 2A. The amino acid sequence of Sub 1 is shown in Table 2B and t DNA sequence in Table 2C. 2. HIV 18 Kd fusion protein denoted Sub 2. The amino acid sequence of the HI portion of Sub 2 is shown in Table 3 and the DNA sequence of the HIV portion Sub 2 in Table 3A The entire amino acid sequence of Sub 2 is shown in Table 3 and the entire DNA sequence in Table 3C. 3. HTV 27 Kd fusion protein denoted PB1 RF . The amino acid sequence of the HI portion of PBIRF is listed in Table 4 and the DNA sequence of the HIV portion PBIRF is listed in Table 4A. The entire amino acid sequence and DNA sequence PB1 RF are in Tables 4B and 4C, respectively. 4. HIV 28 Kd fusion protein denoted PB1 MN . The amino acid sequence of the HI portion of PBIMN is shown in Table 5 and the DNA sequence of the HIV portio of PBlj dN is shown in Table 5A. The entire amino acid sequence and DNA sequenc of PBIMN are shown in Tables 5B and 5C, respectively. 5. HIV 26 Kd fusion protein denoted PBlsc- The amino acid sequence of the HI portion of PB1 SC is listed in Table 6 and the DNA sequence of the HIV portion Blsc i s shown in Table 6A. The entire amino acid sequence and DNA sequenc of PBl S c are shown in Tables 6B and 6C, respectively. 6. HIV 26 Kd fusion protein denoted PB1 W J2- Th* 2 amino acid sequence of the HT portion of PBI-WMJ-J is listed in Table 7 and the DNA sequence of the HIV portio of PB1- WMJ2 is shown in Table 7A. The entire amino acid sequence and DN sequence of PB1- WMI2 are shown in Tables 7B and 7C, respectively. B. Synthetic Peptides Comprising Segments of the Principal Neutralizing Domain From HI Variants The amino acid cysteine in parentheses is added for the purpose of crosslinking to carri proteins. Also, where the peptides have cysteines at or near both ends, these cysteines can form disulfide bond, thus giving the peptides a loop-like configuration. For any of these peptides which d not have cysteines at or near both ends, cysteines may be added if a loop-like configuration is desire The loop configuration can be utilized to enhance the immunogenic properties of the peptides. Oth amino acids in parentheses are immunologically silent spacers. Pentide 135 (from isolate HIV-III B ): Asn Asn Thr Arg Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Ala Phe Val Thr He Gly Lys He Gly (Cys) Peptide 136 (from isolate HIV-IIIB): Leu Asn Gin Ser Val Glu He Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Ala Phe Val Thr He Gly Lys He Gly Asn Met Peptide 139 (from isolate HIV-RF): Asn Asn Thr Arg Lys Ser He Thr Lys Gly Pro Gly Arg Val He Tyr Ala Thr Gly Gin He He Gly (Cys) Peptide 141 (from isolate HIV-WMJ2): Asn Asn Val Arg Arg Ser Leu Ser He Gly Pro Gly Arg Ala Phe Arg Thr Arg Glu He He Gly (Cys) Peptide 142 (from isolate HIV-MN): Tyr Asn Lys Arg Lys Arg He His He Gly Pro Gly Arg Ala Phe Tyr Thr Thr Lys Asn He He Gly (Cys) Peptide 143 (from isolate HIV-SC): Asn Asn Thr Thr Arg Ser He His He Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp He He Gly (Cys) Peptide 131 (from isolate HIV-IIIB): (Tyr) C s Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser He Arg He Gin Arg Gly Peptide 132 (from isolate HIV-IIIB): Pro Gly Arg Ala Phe Val Thr He Gly Lys He Gly Asn Met Arg Gin Ala His Cys (Tyr) Peptide 134 (from isolate HIV-IIIB): Glu Arg Val Ala Asp Leu Asn Gin Ser Val Glu He Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser He Peptide 339 (from isolate HIV-RF): He Thr Lys Gly Pro Gly Arg Val He Tyr (Cys) RP341 (from isolate HIV-WMJ2): Leu Ser He Gly Pro Gly Arg Ala Phe Arg (Cys) RP343 (from isolate HIV-SC): He His He Gly Pro Gly Arg Ala Phe Tyr (Cys) RP60 (from isolate HIV-IIIB): He Asn Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser He RP335 (from isolate HIV-IIIB): He Gin Arg Gly Pro Gly Arg Ala Phe (Cys) RP337 (from isolate HIV-IIIB): Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Ala Phe (Cys) RP77 (from isolate HIV-IIIB): Gly Pro Gly Arg Ala Phe RP83 (from isolate HIV-WMJ1): His He His He Gly Pro Gly Arg Ala Phe Tyr Thr Gly (Cys) RP79 (from isolate HIV-IIIB): Gin Arg Gly Pro Gly Arg Ala Phe (Cys) RP57: He Asn Cys Thr Arg Pro Ala His Cys Asn He Ser RP55: Ala His Cys Asn He Ser RP75A: (Ala Ala Ala Ala Ala Ala) Gly Pro Gly Arg (Ala Ala Ala Ala Ala Cys) RP56: He Asn Cys Thr Arg Pro RP59: He Gly Asp He Arg Gin Ala His Cys Asn He Ser RP342 (from isolate HIV-MN): He His He Gly Pro Gly Arg Ala Phe Tyr Thr (Cys) RP96 (HIV-MN related): (Cys) Gly He His He Gly Pro Gly Arg Ala Phe Tyr Thr (Cys) RP97 (HIV-MN related): (Ser Gly Gly) He His He Gly Pro Gly Arg Ala Phe Tyr (Gly Gly Ser Cys) RP98 (HIV-MN related): (Cys Ser Gly Gly) He His He Gly Pro Gly Arg Ala Phe Tyr (Gly Gly Ser Cys) RP99 (HIV-MN related): (Cys Ser Gly Gly) He His He Gly Pro Gly Arg Ala Phe Tyr (Gly Gly Ser) RP100: (Ser Gly Gly) Thr Arg Lys Gly He His He Gly Pro Gly Arg Ala He Tyr (Gly Gly Ser Cys) RP102: (Ser Gly Gly) Thr Arg Lys Ser He Ser He Gly Pro Gly Arg Ala Phe (Gly Gly Ser Cys) RP91 (MN-Hepatitis fusion): Arg He His He Gly Pro Gly Arg Ala Phe Tyr Gly Phe Phe Leu Leu Thr Arg He Leu Thr He Pro Gin Ser Leu Asp (Cys) RP104: (Ser Gly Gly) He Gly Pro Gly Arg Ala Phe Tyr Thr Thr Lys (Gly Gly Ser Cys) RP106: (Ser Gly Gly) Arg He His He Gly Pro Gly Arg Ala Phe (Gly Gly Ser Cys) RP108: (Ser Gly Gly) His He Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly (Gly Gly Ser Cys) RP7Q (from isolate HIV-MN): He Asn Cys Thr Arg Pro Asn Tyr Asn Lys Arg Lys Arg He His He Gly Pro Gly Arg Ala Phe Tyr Thr Thr Lys Asn He He Gly Thr He Arg Gin Ala His Cys Asn He Ser RPM (from isolate HIV-MN): He His He Gly Pro Gly Arg Ala Phe Tyr Thr Gly (Cys) RP144 (from isolate 7887-3): Asn Asn Thr Ser Arg Gly He Arg He Gly Pro Gly Arg Ala He Leu Ala Thr Glu Arg He He Gly (Cys) RP145 (from isolate 6587-7): Asn Asn Thr Arg Lys Gly He His He Gly Pro Gly Arg Ala Phe Tyr Ala Thr Gly Asp He He Gly (Cys) RP146 (from isolate CC): Asn Asn Thr Lys Lys Gly He Arg He Gly Pro Gly Arg Ala Val Tyr Thr Ala Arg Arg He He Gly (Cys) RP147 (from isolate KK261): Asn Asn Thr Arg Lys Gly He Tyr Val Gly Ser Gly Arg Lys Val Tyr Thr Arg His Lys He He Gly (Cys) RP150 (from isolate ARV-2): Asn Asn Thr Arg Lys Ser He Tyr He Gly Pro Gly Arg Ala Phe His Thr Thr Gly Arg He He Gly (Cys) RP151 (from isolate NY5): Asn Asn Thr Lys Lys Gly He Ala He Gly Pro Gly Arg Thr Leu Tyr Ala Arg Glu Lys He He Gly (Cys) C. Hybrid Peptides Containing Sequences from More Than One Variant RP73 (from isolates HTV-IIIB, HTV-RF): Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Val He Tyr (Cys) RP74 (from isolates HTV-IIIB, HTV-RF, HTV-MN, HIV-SC): Arg He His He Gly Pro Gly Arg Ala Phe Tyr Ala Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Val He Tyr (Cys) RP80 (from isolates HTV-IIIB, HTV-RF): Arg He Gin Arg Gly Pro Gly Arg Val He Tyr Ala Thr (Cys) RP81 (from isolates HTV-IIIB, HIV-RF, HIV-WMJl, HIV-MN): Arg He His He Gly Pro Gly Arg Ala Phe Tyr Thr Gly Arg He Gin Arg Gly Pro Gly Arg Val He Tyr Ala Thr (Cys) RP82 (from isolates HTV-MN, HIV-WMJ1): Arg He His He Gly Pro Gly Arg Ala Phe Tyr Thr Gly (Cys) RP88 (from isolates HIV-MN, HTV-SC): Ser He His He Gly Pro Gly Arg Ala Phe Tyr Thr Thr Gly (Cys) RP137 (from isolates HTV-IIIB, HTV-RF): Asn Asn Thr Arg Lys Ser He Arg He Thr Lys Gly Pro Gly Arg Ala Phe Val Thr He Gly Lys He Gly (Cys) RP14Q (from isolates HTV-IIIB, HTV-RF): Asn Asn Thr Arg Lys Ser He Thr Lys Gly Pro Gly Arg Ala Phe Val Thr He Gly Lys He Gly (Cys) Peptide 64 (from isolates HIV-IIIB, HIV-RF, HIV-MN, HTV-SC): Arg He His He Gly Pro Gly Arg Ala He Phe Tyr Arg He Gin Arg Gly Pro Gly Arg Val He Tyr (Cys) Peptide 338 (from isolates HTV-IIIB, HTV-RF): Arg He Gin Arg Gly Pro Gly Arg Val He Tyr (Cys) Peptide 138 (from isolates HTV-IIIB, HTV-RF): Asn Asn Thr Arg Lys Ser He Arg He Gin Arg Gly Pro Gly Arg Val He Tyr Ala Thr Gly Lys He Gly (Cys) RP63 (III B -RF hybrid): Arg He Gin Arg Gly Pro Gly Arg Val He Tyr (Cys) D. Miscellaneous Peptide Sequences RP41: Gly Pro Gly Arg RP61: Gly Pro Gly Arg (Ala Ala Ala Ala Ala Ala Cys) RP75: (Cys Ala Ala Ala Ala Ala) Gly Pro Gly Arg Ala Phe (Ala Ala Ala Cys) RP111: He Gin Arg Gly Pro Gly He Gin Arg Gly Pro Gly (Cys) RP113: Gin Arg Gly Pro Gly Arg Gin Arg Gly Pro Gly Arg Gin Arg Gly Pro Gly Arg (Cys) RP114: Arg Gly Pro Gly Arg Gly Pro Gly Arg Gly Pro Gly Arg Gly Pro Gly Arg (Cys) RP116: Gly Pro Gly Arg Ala Phe Gly Pro Gly Arg Ala Phe Gly Pro Gly Arg Ala Phe (Cys) RP120: Ser He Arg He Gly Pro Gly Arg Ala Phe Tyr Thr (Cys) RP121c: (Cys) Gly Pro Gly Arg (Cys) RP122c: (Cys) He Gly Pro Gly Arg Ala (Cys) RP123c: (Cys) His He Gly Pro Gly Arg Ala Phe (Cys) The proteins and peptides exemplifying the subject invention can be made by well-know synthesis procedures. Alternatively, these entities can be made by use of recombinant DN procedures. Such recombinant DNA procedures are disclosed herein since they were, in fact, th procedures initially utilized to obtain the novel proteins and peptides of the invention. However, onc these entities were prepared and their molecules sequenced, it is apparent to a person skilled in th art that the preferred method for making them would now be by chemical synthesis means. Fo example, there are available automated machines which can readily make proteins and peptides of th molecular sizes disclosed herein. In the recombinant DNA procedures for making some of the proteins and peptides of th invention, an expression vector plasmid denoted pREV2.2 was used. This plasmid was initiall constructed from a plasmid denoted pBGl. Plasmid pBGl is deposited in the R coli host MS371 with the Northern Regional Researc Laboratory (NRRL, U.S. Department of Agriculture, Peoria, Illinois, USA). It is in the permanen collection of this repository. E. coli MS371(pBGl), NRR1 B-15904, was deposited on November 1 1984. R coli MS371, NRRL B-15129 is now available to the public. Plasmid pREV2.2 was deposited in the R coli JM103 host with NRRL on July 30, 1986. coli JM103(pREV2.2) received the accession number NRRL B-18091. NRRL B-15904 and NRR B-18091 will be available, without restrictions, to the public upon the grant of a patent which disclose them. Other R coli strains, disclosed herein, were deposited as follows: R coli SG20251, NRRL B-15918, was deposited on December 12, 1984. R coli CAG629(pKHl), NRRL B-18095, was deposited on July 30, 1986. This latter deposit can be subjected to standard techniques to separate the plasmid from th host cell, and, thus, use the host R cρji CAG629 as disclosed herein. The subject cultures have been deposited under conditions that assure that access to th cultures will be available during the pendency of the patent application disclosing them to on determined by the Commissioner of Patents and Trademarks to be entitled thereto under 37 CFR 1.1 and 35 USC 122. The deposits are available as required by foreign patent laws in countries wherei counterparts of the subject application, or its progeny, are filed. However, it should be understoo that the availability of a deposit does not constitute a license to practice the subject invention i derogation of patent rights granted by governmental action. Further, the subject culture deposits will be stored and made available to the public in accor with the provisions of the Budapest Treaty for the Deposit of Microorganisms, i.e., they will be store with all the care necessary to keep them viable and uncontaminated for a period of at least five year after the most recent request for the furnishing of a sample of the deposits, and in any case, for period of at least 30 (thirty) years after the date of deposit or for the enforceable life of any paten which may issue disclosing the cultures. The depositor acknowledges the duty to replace the deposit should the depository be unable to furnish a sample when requested, due to the condition of th deposits. All restrictions on the availability to the public of the subject culture deposits will b irrevocably removed upon the granting of a patent disclosing them. The novel HIV proteins and peptides of the subject invention can be expressed i Saccharomvces cerevisiae using plasmids containing the inducible galactose promoter from thi organism (Broach, J.R., Y. Li, L.C. Wu, and M. Jayaram [1983] in Experimental Manipulation of Gen Expression, p. 83, ed. M. Inouye, Academic Press). These plasmids are called YEp51 and YEp5 (Broach, J.R. et al [1983]) and contain the R coli origin of replication, the gene for actamase, th yeast LEU2 gene, the 2 / m origin of replication and the 2 /mi circle REP3 locus. Recombinant gen expression is driven by the yeast GAL10 gene promoter. Yeast promoters such as galactose and alcohol dehydrogenase (Bennetzen, J.L and B.D. Hal [1982] J. Biol. Chem. 257:3018; Ammerer, G. [1983] in Methods in Enzymology Vol. 101, p. 192) phosphoglycerate kinase (Derynck, R., R.A. Hitzeman, P.W. Gray, D.V. Goeddel [1983] i Experimental Manipulation of Gene Expression, p. 247, ed. M. Inouye, Academic Press), trios phosphate isomerase (Alber, T. and G. Kawasaki [1982] J. Molec and Applied Genet. 1:419), o enolase (Innes, M.A. et al. [1985] Science 226:21) can be used. The genes disclosed herein can be expressed in simian cells. When the genes encoding thes proteins are cloned into one of the plasmids as described in Okayama and Berg (Okayama, H. an P. Berg [1983] Molec. and Cell. Biol. 3:280) and references therein, or COS cells transformed wit these plasmids, synthesis of HTV proteins can be detected immunologically. Other mammalian cell gene expression protein production systems can be used. Examples o other such systems are the vaccinia virus expression system (Moss, B. [1985] Immunology Today 6:24 Chakrabarti, S., K. BrechUng, B. Moss [1985] Molec. and Cell. Biol. 5:3403) and the vectors derive from murine retroviruses (Mulligan, R.C [1983] in Experimental Manipulation of Gene Expressio p. 155, ed. M. Inouye, Academic Press). The HIV proteins and peptides of the subject invention can be chemically synthesized by soli phase peptide synthetic techniques such as BOC and FMOC (Merrifield, R.B. [1963] J. Amer. Che Soc 85:2149; Chang, C. and J. Meienhofer [1978] Int. J. Peptide Protein Res. 11:246). As is well known in the art, the amino acid sequence of a protein is determined by th nucleotide sequence of the DNA. Because of the redundancy of the genetic code, i.e., more than on coding nucleotide triplet (codon) can be used for most of the amino acids used to make protein different nucleotide sequences can code for a particular amino acid. Thus, the genetic code can b depicted as follows: Key: Each 3-letter deoxynucleotide triplet corresponds to a trinucleotide of mRNA, having a 5'-en on the left and a 3'-end on the right. All DNA sequences given herein are those of the strand whos sequence corresponds to the mRNA sequence, with thymine substituted for uracil. The letters stan for the purine or pyrimidine bases forming the deoxynucleotide sequence. A = adenine G = guanine C = cytosine T = thymine X = T or C if Y is A or G X = CifYisCorT Y = A, G, C or T if X is C Y = A or G if X is T W = C or A if Z is A or G W = CifZisCorT Z = A, G, C or T if W is C Z = AorGifWisA QR = TC if S is A, G, C or T; alternatively QR = AG if S is T or C J = A or G K = T or C L = A, T, C or G M = A, C or T The above shows that the novel amino acid sequences of the HIV proteins and peptides o the subject invention can be' prepared by nucleotide sequences other than those disclosed herein Functionally equivalent nucleotide sequences encoding the novel amino acid sequences of these HI proteins and peptides, or fragments thereof having HTV antigenic or immunogenic or therapeuti activity, can be prepared by known synthetic procedures. Accordingly, the subject invention include such functionally equivalent nucleotide sequences. Thus the scope of the subject invention includes not only the specific nucleotide sequence depicted herein, but also all equivalent nucleotide sequences coding for molecules with substantiall the same HTV antigenic or immunogenic or therapeutic activity. Further, the scope of the subject invention is intended to cover not only the specific amin acid sequences disclosed, but also similar sequences coding for proteins or protein fragments havin comparable ability to induce the formation of and/or bind to specific HIV antibodies possessing th properties of virus neutraϋzation. The term "equivalent" is being used in its ordinary patent usage here as denoting a nucleotid sequence which performs substantially as the nucleotide sequence identified herein to produc molecules with substantially the same HTV antigenic or immunogenic or therapeutic activity i essentially the same kind of hosts. Within this definition are subfragments which have HIV antigeni or immunogenic or therapeutic activity. As disclosed above, it is well within the skill of those in the genetic engineering art to use th nucleotide sequences encoding HTV antigenic or immunogenic or therapeutic activity of the subje invention to produce HTV proteins via microbial processes. Fusing the sequences into an expressio vector and transforming or transfecting into hosts, either eukaryotic (yeast or mammalian cells) prokaryotic (bacterial cells), are standard procedures used in producing other well-known proteins, e.g insulin, interferons, human growth hormone, IL-1, IL-2, and the like. Similar procedures, or obvio modifications thereof, can be employed to prepare HTV proteins or peptides by microbial means tissue-culture technology in accord with the subject invention. The nucleotide sequences disclosed herein can be prepared by a "gene machine" by procedur well known in the art. This is possible because of the disclosure of the nucleotide sequence. The restriction enzymes disclosed can be purchased from Bethesda Research Laboratorie Gaithersburg, MD, or New England Biolabs, Beverly, MA The enzymes are used according to t instructions provided by the supplier. The various methods employed in the preparation of the plasmids and transformation of ho organisms are well known in the art. These procedures are all described in Maniatis, T., E.F. Fritsc and J. Sambrook (1982) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laborator New York. Thus, it is within the skill of those in the genetic engineering art to extract DNA fro microbial cells, perform restriction enzyme digestions, electrophorese DNA fragments, tail and anneal plasmid and insert DNA, ligate DNA, transform cells, e.g., R coli cells, prepare plasmid DNA, electrophorese proteins, and sequence DNA. Immunochemical assays employing the HIV proteins or peptides of the invention can take a variety of forms. One preferred type is a liquid phase assay wherein the HIV antigen and the sample to be tested are mixed and allowed to form immune complexes in solution which are then detected by a variety of methods. Another preferred type is a solid phase immunometric assay. In solid phas assays, an HIV protein or peptide is immobilized on a solid phase to form an antigen immunoadsorbent. The immunoadsorbent is incubated with the sample to be tested. After an appropriate incubation period, the immunoadsorbent is separated from the sample, and labeled anti (human IgG) antibody is used to detect human anti-HTV antibody bound to the immunoadsorbent. The amount of label associated with the immunoadsorbent can be compared to positive and negativ controls to assess the presence or absence of anti-HTV antibody. The immunoadsorbent can be prepared by adsorbing or coupling a purified HIV protein o peptide to a solid phase. Various solid phases can be used, such as beads formed of glass, polystyrene polypropylene, dextran or other material. Other suitable solid phases include tubes or plates forme from or coated with these materials. The HTV proteins or peptides can be either covalently or non-covalently bound to the soli phase by techniques such as covalent bonding via an amide or ester linkage or adsorption. Afrer th HTV protein or peptide is affixed to the solid phase, the solid phase can be post-coated with an anima protein, e.g., 3% fish gelatin. This provides a blocking protein which reduces nonspecific adsorptio of protein to the immunoadsorbent surface. The immunoadsorbent is then incubated with the sample to be tested for anti-HIV antibody In blood screening, blood plasma or serum is used. The plasma or serum is diluted with norma animal plasma or serum. The diluent plasma or serum is derived from the same animal species tha is the source of the anti-(human IgG) antibody. The preferred anti-(human IgG) antibody is goa anti-(human IgG) antibody. Thus, in the preferred format, the diluent would be goat serum or plasma The conditions of incubation, e.g., pH and temperature, and the duration of incubation ar not crucial. These parameters can be optimized by routine experimentation. Generally, the incubatio will be run for 1-2 hr at about 45°C in a buffer of pH 7-8. After incubation, the immunoadsorbent and the sample are separated. Separation can b accomplished by any conventional separation technique such as sedimentation or centrifugation. Th immunoadsorbent then may be washed free of sample to eliminate any interfering substance. The immunoadsorbent is incubated with the labeled anti-(human IgG) antibody (tracer) t detect human antibody bound thereto. Generally the immunoadsorbent is incubated with a solutio of the labeled anti-(human IgG) antibody which contains a small amount (about 1%) of the seru or plasma of the animal species which serves as the source of the anti-(human IgG) antibody. Anti (human IgG) antibody can be obtained from any animal source. However, goat anti-(human IgG antibody is preferred. The anti-(human IgG) antibody can be an antibody against the Fc fragment o human IgG, for example, goat anti-(human IgG) Fc antibody. The anti-(human IgG) antibody or anti-(human IgG) Fc can be labeled with a radioactiv material such as 125 I; labeled with an optical label, such as a fluorescent material; or labeled with a enzyme such as horseradish peroxidase. The anti-human antibody can also be biotinylated and labele avidin used to detect its binding to the immunoadsorbent. After incubation with the labeled antibody, the immunoadsorbent is separated from th solution and the label associated with the immunoadsorbent is evaluated. Depending upon the choic of label, the evaluation can be done in a variety of ways. The label may be detected by a gamm counter if the label is a radioactive gamma emitter, or by a fluorimeter, if the label is a fluorescen material. In the case of an enzyme, label detection may be done colorimetrically employing a substrat for the enzyme. The amount of label associated with the immunoadsorbent is compared with positive an negative controls in order to determine the presence of anti-HTV antibody. The controls are generall run concomitantly with the sample to be tested. A positive control is a serum containing antibod against HTV; a negative control is a serum from healthy individuals which does not contain antibod against HTV. For convenience and standardization, reagents for the performance of the immunometric assa can be assembled in assay kits. A kit for screening blood, for example, can include: (a) an immunoadsorbent, e.g., a polystyrene bead coated with an HIV protein or peptid (b) a diluent for the serum or plasma sample, e.g. normal goat serum or plasma; (c) an anti-(human IgG) antibody, e.g., goat anti-(human IgG) antibody in buffere aqueous solution containing about 1% goat serum or plasma; (d) a positive control, e.g., serum containing antibody against at least one of the nov HTV proteins or peptides; and (e) a negative control, e.g., pooled sera from healthy individuals which does not contai antibody against at least one of the novel HIV proteins or peptides. If the label is an enzyme, an additional element of the kit can be the substrate for the enzym Another type of assay for anti-HTV antibody is an antigen sandwich assay. In this assay, labeled HIV protein or peptide is used in place of anti-(human IgG) antibody to detect anti-HI antibody bound to the immunoadsorbent. The assay is based in principle on the bivalency of antibod molecules. One binding site of the antibody binds the antigen affixed to the solid phase; the secon is available for binding the labeled antigen. The assay procedure is essentially the same as described for the immunometric assay except that after incubation with the sample, the immunoadsorbent is incubated with a solution of labeled HTV protein or peptide. HTV proteins or peptides can be labeled with radioisotope, an enzyme, etc. for this type of assay. In a third format, the bacterial protein, protein A, which binds the Fc segment of an IgG molecule without interfering with the antigen-antibody interaction can be used as the labeled tracer to detect anti-HTV antibody adsorbed to the immunoadsorbent. Protein A can be readily labeled with a radioisotope, enzyme, or other detectable species. Immunochemical assays employing an HTV protein or peptide have several advantages ove those employing a whole (or disrupted) virus. Assays based upon an HIV protein or peptide will alleviate the concern over growing large quantities of infectious virus and the inherent variabili associated with cell culturing and virus production. Further, the assay will help mitigate the real o perceived fear of contracting AIDS by technicians in hospitals, clinics and blood banks who perform the test. Immunochemical assays employing recombinant envelope proteins from multiple viral variant have additional advantages over proteins from a single HIV variant. Assays incorporating protei sequences from multiple variants are more likely to accurately survey antibodies in the huma population infected with diverse HTV variants. Also, solid phase enzyme-Hnked immunosorbent assa (ELISA) utilizing different HTV variant proteins would allow determination of prevalent serotypes i different geographic locations. This determination has not been possible until now as no availabl antibody detection kit utilizes more than one HTV variant Another use of recombinant proteins from HIV variants is to elicit variant-specific antiser in test animals. This antiserum would provide a reagent to identify which viral variant infected a individual. Currently, "virus typing" can only be done by viral gene cloning and sequencing. Bindin of variant-specific serum to a patient viral isolate would provide a means of rapid detection no currently available. For example, sera raised to the proteins denoted PB1 Π IB . PBIRF- PB1 MN- Pβ lsc and PB1- WMJ2 ∞ 11 be used to screen viral isolates from patients to determine which HIV variant th clinical isolate most closely resembles. This "screening" can be done by a variety of known antibody antigen binding techniques. Vaccines comprising one or more of the HIV proteins or peptides, disclosed herein, an variants thereof having antigenic properties, can be prepared by procedures well known in the art For example, such vaccines can be prepared as injectables, e.g., liquid solutions or suspensions. Soli forms for solution in, or suspension in, a liquid prior to injection also can be prepared. Optionally the preparation also can be emulsified. The active antigenic ingredient or ingredients can be mixe with excipients which are pharmaceutically acceptable and compatible with the active ingredient Examples of suitable excipients are water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof. In addition, if desired, the vaccine can contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, or adjuvants such as aluminum hydroxide or muramyl dipeptide or variations thereof. In the case of peptides, coupling to larger molecules such as KLH sometimes enhances iramunogenicity. The vaccines are conventionally administered parenterally, by injection, for example, either subcutaneously or intramuscularly. Additional formulations which are suitable for other modes of administration include suppositories and, in some cases, oral formulations. For suppositories, traditional binders and carriers include, for example, polyalkalene glycols or triglycerides. Suppositories can be formed from mixtures containing the active ingredient in the range of about 0.5% to about 10%, preferably about 1 to about 2%. Oral formulations can include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like. These compositions can take the form of solutions, suspensions, tablets, pills, capsules, sustained release formulations or powders and contain from about 10% to about 95% of active ingredient, preferably from about 25% to about 70%. The compounds can be formulated into the vaccine as neutral or salt forms. Pharmaceutically acceptable salts include the acid addition salts (formed with the free amino groups of the peptide) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxy groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, 2-ethylamin ethanol, histidine, procaine, and the Hke. A vaccine composition may include peptides containing helper cell epitopes in combination with protein fragments containing the principal neutralizin domain. Several of these epitopes have been mapped within the HTV envelope, and these regions hav been shown to stimulate proUferation and lymphokine release from lymphocytes. Providing both o these epitopes in a vaccine may result in the stimulation of both the humoral and the cellular immun responses. Alternatively, a vaccine composition may include a compound which functions to increase th general immune response. One such compound is interleukin-2 (IL-2) which has been reported t enhance immunogenicity by general immune stimulation (Nunberg et al. [1988] In New Chemical an Genetic Approaches to Vaccination. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). IL 2 may be coupled with an HIV peptide or protein comprising the PND to enhance the efficacy o vaccination. The vaccines are administered in a manner compatible with the dosage formulation, and i such amount as will be therapeutically effective and immunogenic. The quantity to be administere depends on the subject to be treated, capacity of the subject's immune system to synthesize antibodie and the degree of protection desired. Precise amounts of active ingredient required to be administere depend on the judgment of the practitioner and are peculiar to each individual. However, suitabl dosage ranges are of the order of about several hundred micrograms active ingredient per individua Suitable regimes for initial administration and booster shots are also variable, but are typified by a initial administration foUowed in one or two week intervals by a subsequent injection or othe administration. HTV is known to undergo amino acid sequence variation, particularly in the envelope gen (Starcich, B.R. [1986] Cell 45:637-648; Hahn, B.H. et al. [1986] Science 232:1548-1553). Over 10 variants have been analyzed by molecular cloning and restriction enzyme recognition analysis, an several of these have been analyzed by nucleotide sequencing. Some of these are the HIV isolate known as RF (Popovic, M. et al. [1984] Science 224:497-500), WMJ-1 (Hahn, B.H. et al. [198 Science 232:1548-1553), LAV (Wain-Hobson, S. et al. [1985] Cell 40:9-17), and ARV-2 (Sanche Pescador, R. et al. [1985] Science 227:484-492). HTV peptides from different viral isolate can be used in vaccine preparations to protect against infections by different HTV isolates. Furthe a vaccine preparation can be made using more than one envelope protein fragment corresponding t the principal neutralizing domain of more than one HTV isolate to provide immunity and thus giv better protection against AIDS. Alternatively, the vaccine preparation can be made using a singl protein fragment that is comprised of a tandem arrangement of principal neutralizing epitopes fro more than one HTV isolate. By identifying the principal neutralizing domain of HIV, this polypeptid region can be applied to formulate valuable vaccine, diagnostic, and therapeutic reagents. Antibodies to recombinant peptides disclosed herein are useful as therapeutic and prophylact reagents. The generation of polyclonal or monoclonal antibodies capable of neutralizing a variety HTV variants could be used to reduce the incidence of accidental infection and treat HIV infecte people that are immuno-compromised. Additionally, immunization regimens may elicit polyclonal ser capable of broadly neutralizing several variants of HTV. The ability to neutralize multiple HI variants is termed broadly neutralizing antibody. Broadly neutralizing antibody may neutralize two more HIV variants or all HTV variants. Therefore, a mixture of broadly neutralizing antibodies th neutralize different groups of HIV variants would be useful for diagnosis, prophylaxis, and therapy AIDS. It is surprising and advantageous that immunization with peptides from five HIV varian would yield sera capable of neutralizing more than these five HIV variants when immunization wit two does not. Example 22 shows that immunization with five peptides elicits broadly neutralizing ser Broadly neutralizing sera may also be generated if several sequences from the hypervariable region diverse HTV variants are presented as a single synthetic peptide. Additionally, one may elicit th broadly neutralizing sera by reimmunization of animals primed with RP136 or equivalent proteins wit peptides containing only the conserved amino acids within this hypervariable region. Thes immunization regimens would be useful for vaccination and for deriving antibodies useful a therapeutic agents. Polyvalent immune globulin for use in passive immunization can be prepared by immunizatio of horses or by poofing immune human sera and fractionation of the IgG component from plasma o sera. Human or mouse monoclonal antibody producing cell lines may be prepared by standar transformation and hybridoma technology (Methods in Enzvmoloev. Vol. 121, Sections I and II [198 eds. J.J. Langone and H.V. Vunakis, Academic Press). HTV monoclonal antibody can be prepared i accord with the procedures disclosed by Matsushita et al. (Matsushita et al. [1988] Journal of Virolog 62(6):2107-2114). Since, for the most part, monoclonal antibodies are produced in species other tha humans, they are often immunogenic to humans. In order to successfully use these monoclon antibodies in the treatment of humans, it may be necessary to create a chimeric antibody molecul wherein the portion of the polypeptide involved with figand binding (the variable region) is derive from one species, and the portion involved with providing structural stabflity and other biologic functions (the constant region) is derived from a human antibody. Methods for producing chime antibodies in which the variable domain is derived from one host and the constant domain is derive from a second host are well known to those skilled in the art. See, for example, Neuberger et a WO Publication No. 8601533, priority 93/84; Morrison et al., EP Publication No. 0 173 494, priori 8/27/84. An alternative method, in which an antibody is produced by replacing only t complementarity determining regions (CDRs) of the variable region with the CDRs from a immunoglobulin of the desired antigenic specificity, is described by Winter (GB Publication No. 2 1 638, priority 3 2786). Murine monoclonals can be made compatible with human therapeutic use producing an antibody containing a human Fc portion (Morrison, S.L. [1985] Science 229:1202-1207 Established procedures would allow construction, expression, and purification of such a hyb monoclonal antibody. Regimens for administering immune globulin therapeutically have previous been used for a number of infectious diseases. As used herein, the term "antibody" is meant to encompass monoclonal or polyclon antibodies, whole, intact antibodies or antibody fragments having the immunological activity of t whole antibody. Also encompassed within the term "antibody" are chimeric antibodies having t variable and constant regions from different host species, or those wherein only the CDRs a replaced. For treatment of HTV infection, compositions comprising antibodies may be administered an individual or animal in need of treatment. Alternatively, the HIV antigens described here may administered in order to stimulate the recipient's own immune response. When treating with an HI antigen, a single antigen may be administered or, preferably, a broadly neutralizing anligen or mixtu of antigens may be administered. Such compositions are described in detail in the examples whic follow. The ability to modify peptides made by organic synthesis can be advantageous for diagnostic therapeutic, and prophylactic use by improving efficiency of immobilization, increasing protein stability increasing immunogenicity, altering immunogenicity, reducing toxicity, or allowing multiple variation simultaneously. For example, peptides can be modified to increase or decrease net charge b modification of amino or carboxyl groups (carbamylation, trifluoroacetylation or succinylation of amin groups; acetylation of carboxyl groups). Peptides can be made more stable by, for example, inclusio of D-amino acids or circularization of the peptide. Reductive state of peptides can be altered by, fo example, sulfonation of cystinyl groups. Peptides can also be modified covalently or non-covalentl with non-proteinaceous materials such as lipids or carbohydrates to enhance immunogenicity o solubility. Polyethylene glycol can be used to enhance solubility. The subject invention includes al such chemical modifications of the proteins and peptides disclosed herein so long as the modifie protein and/or peptide retains substantially all the antigenic/immunogenic properties of the paren compound. Peptides can also be modified to contain antigenic properties of more than one viral variant This has been done, for example, with Foot and Mouth Disease virus. Foot and Mouth Disease virus is similar to HIV in that multiple variants exist an immunization with one variant does not lead to protection against other variants. The real utility o peptides as immunogens is demonstrated by eliciting immunity to more than one variant b modification of the peptide to possess properties of both natural variants. When such a modifie variant was used to immunize test animals, they were protected against both Foot and Mouth viru strains A10 and A12 (Brown, F. in Virus Vaccines, ed. G. Dreesman, J. Branson, R. Kennedy, pp.49 54 [1985]). HIV peptides or proteins containing a PND epitope can also be coupled with or incorporate into an unrelated virus particle, a replicating virus, or other microorganism in order to enhanc immunogenicity. The HIV epitope may be genetically or chemically attached to the viral particle o microorganism or an immunogenic portion or component thereof. Antigenic epitopes have bee attached to viral proteins or particles to enhance the immune response. For example, the VP6 capsi protein of rotavirus has been used as an immunologic carrier protein for an epitope of interest eithe in the monomeric form or as oligomers of VP6 in the form of particles (EP Publication No. 0 25 149). Similarly, Evans et al. (1989, Nature 339:385) have constructed chimaeras of the polioviru capsid protein and an epitope of HIV gp41 to enhance immunogenicity of the HIV epitope. Foreig antigenic determinants have also been expressed and presented by bacterial cells. A Salmonella strai expressing a cloned Salmonella flagellin gene, into which was inserted an epitope of either choler toxin or hepatitis B surface antigen, was reported to elicit both cellular and humoral responses to th inserted epitopes (Newton et al. [1989] Science 244:70-72; and Wu et al. [1989] Proc. Natl. Acad. Sc 86:4726-4730). Example 18 shows that a peptide containing amino acid sequences from two HIV variants ca block virus neutralization activity of two virus specific neutralizing antisera. This suggests that peptide or protein containing sequences of two or more HTV variants can elicit an immune respons effective against two or more HTV variants. Example 19 shows that co-immunization with envelope proteins from two HIV isolates elici an immune response capable of neutralizing two HTV isolates. This suggests that co-immunizati with proteins from two or more HIV variants can eHcit an immune response effective against two more HTV variants. Following are examples which illustrate the process of the invention, including the best mod These examples should not be construed as limiting. All solvent mature proportions are by volu unless otherwise noted. Example 1 - Construction of plasmid pREV2.2 The pREV2.2 plasmid expression vector was constructed from plasmid pBGl. Plasmid pB can be isolated from its E. coli host by weH known procedures, e.g., using cleared lysate-isopycn density gradient procedures, and the Hke. Like pBGl, pREV2Λ expresses inserted genes behind t R coli promoter. The differences between pBGl and pREV2.2 are the following: 1. pREV2.2 lacks a functional replication of plasmid (rop) protein. 2. pREV2.2 has the trpA transcription terminator inserted into the AatH site. T sequence insures transcription termination of over-expressed genes. 3. pREV2.2 has genes to provide resistance to ampicillin and chloramphenicol, where pBGl provides resistance only to ampicillin. 4. pREV2.2 contains a sequence encoding sites for several restriction endonucleases. The following procedures were used to make each of the four changes listed above: la. 5 μg of plasmid pBGl was restricted with Ndel, which gives two fragments approximately 2160 and 3440 base pairs. lb. 0.1 μg of DNA from the digestion mixture, after inactivation of the Ndel. was treat with T4 DNA ligase under conditions that favor intramolecular ligation (200 reaction volume using standard T4 ligase reaction conditions [New England Biola Beverly, MA]). Intramolecular ligation of the 3440 base pair fragment gave ampicillin resistant plasmid. The ligation mixture was transformed into the recipie strain R coli JM103 (available from New England Biolabs) and ampicillin resistan clones were selected by standard procedures. lc. The product plasmid, pBGlΔN, where the 2160 base pair Ndel fragment is delete from pBGl, was selected by preparing plasmid from ampicillin resistant clones an determining the restriction digestion patterns with Ndel and Sail (product fragment approximately 1790 and 1650). This deletion inactivates the rog gene that control plasmid replication. 2a. 5 μg of pBGl N was then digested with EcoRI and Bell and the larger fragmen approximately 2455 base pairs, was isolated. 2b. A synthetic double stranded fragment was prepared by the procedure of Itakura et a (Itakura, K., J.J. Rossi, and R.B. Wallace [1984] Ann. Rev. Biochem. 53:323-356, an references therein) with the following structure: 5' GATCAAGCTTCTGCAGTCGACGCAT 3' TTCGAAGACGTCAGCTGCGTACGCC GCGGATCCGGTACCCGGGAGCTCG 3' TAGGCCATGGGCCCTCGAGCTTAA 5' This fragment has Bell and EcoRI sticky ends and contains recognition sequences fo several restriction endonucleases. 2c 0.1 μg of the 2455 base pair EcoRI-BclI fragment and 0.01 μg of the syntheti fragment were joined with T4 DNA ligase and competent cells of strain JM103 wer transformed. Cells harboring the recombinant plasmid, where the synthetic fragmen was inserted into pBGlΔN between the Bell and EcoRI sites, were selected b digestion of the plasmid with Hpal and EcoRI. The diagnostic fragment sizes ar approximately 2355 and 200 base pairs. This plasmid is called pREVl. 2d. 5 μg of pREVl were digested with Aatll, which cleaves uniquely. 2e. The following double-stranded fragment was synthesized: 5' CGGTACCAGCCCGCCTAATG 3' TGCAGCCATGGTCGGGCGGA AGCGGGClTπTπTGACGT3' TTACTCGCCCGAAAAAAAAC 5' This fragment has Aatll sticky ends and contains the trj>A transcription terminatio sequence. 2f. 0.1 μg of Aatll digested pREVl was ligated with 0.01 μg of the synthetic fragment i a volume of 20 μl using T4 DNA ligase. 2g. Cells of strain JM103, made competent, were transformed and ampicillin resistan clones selected. 2h. Using a Kpnl, EcoRI double restriction digest of plasmid isolated from selecte colonies, a cell containing the correct construction was isolated. The sizes of th Kpnl, EcoRI generated fragments are approximately 2475 and 80 base pairs. Thi plasmid is called pREVITT and contains the trpA transcription terminator. 3a. 5 μg of pREVITT, prepared as disclosed above (by standard methods) was cleave with Ndel and Xmnl and the approximately 850 base pair fragment was isolated. 3b. 5 μg of plasmid pBR325 (BRL, Gaithersburg, MD), which contains the gene conferring resistance to chloramphenicol as well as to ampicillin and tetracycline, wa cleaved with Bell and the ends blunted with Klenow polymerase and dexoynucleotides After inactivating the enzyme, the mixture was treated with Ndel and th approximately 3185 base pair fragment was isolated. This fragment contains the gene for chloramphenicol and ampicillin resistance and the origin of replication. 3c 0.1 μg of the Ndel-Xmnl fragment from pREVITT and the Ndel-Bcll fragment fro pBR325 were Ugated in 20 μl with T4 DNA ligase and the mixture used to transfor competent cells of strain JM103. Cells resistant to both ampicillin an chloramphenicol were selected. 3d. Using an EcoRI and Ndel double digest of plasmid from selected clones, a plasmi was selected giving fragment sizes of approximately 2480, 1145, and 410 base pair This is called plasmid pREVlTT/chl and has genes for resistance to both ampicilli and chloramphenicol. 4a. The foUowing double-stranded fragment was synthesized: MM EcoRV Clal BamHI Sail Hindlll Smal 5' CGAACGCGTGGCCGATATCATCGATGG- ATCCGTCGACAAGCTTCCCGGGAGCT 3' 3' GCTTGCGCACCGGCTATAGTAGCTAC- CTAGGCAGCTGTTCGAAGGGCCC 5' This fragment, with a blunt end and an Sstl sticky end, contains recognition sequence for several restriction enzyme sites. 4b. 5 μg of pREVlTT/chl was cleaved with Nrul (which cleaves about 20 nucleotides fro the Bell site) and Sstl (which cleaves within the multiple cloning site). The larg fragment, approximately 3990 base pairs, was isolated from an agarose gel. 4c 0.1 μg of the Nrul-Sstl fragment from pREVlTT/chl and 0.01 μg of the syntheti fragment were treated with T4 DNA ligase in a volume of 20 μl 4d. This mixture was transformed into strain JM103 and ampicillin resistant clones wer selected. 4e. Plasmid was purified from several clones and screened by digestion with Mlul or Cla Recombinant clones with the new multiple cloning site will give one fragment whe digested with either of these enzymes, because each cleaves the plasmid once. 4f. The sequence of the multiple cloning site was verified. This was done by restrictin the plasmid with Hpal and PvuII and isolating the 1395 base pair fragment, clonin it into the Sjnal site of mpl8 and sequencing it by dideoxynucleotide sequencing usin standard methods. 4g. This plasmid is called pREV2.2. Example 2 - Construction of the bacterial expression vector pREV2.1 Plasmid pREV2.1 was constructed using plasmid pREV2.2 and a synthetic oligonucleotid The resulting plasmid was used to construct pPBl-Sub 1 and pPBl-Sub 2. An example of how to construct pREV2.1 is as follows: 1. Plasmid pREV2.2 is cleaved with restriction enzymes Nrul and BamHI and the 4 K fragment is isolated from an agarose gel. 2. The following double-stranded oligonucleotide is synthesized: 5' CGAACGCGTGGTCCGATATCATCGATG 3' 3' GCTTGCGCACCAGGCTATAGTAGCTACCTAG 5' 3. The fragments from 1 and 2 are Ugated in 20 μl using T4 DNA ligase, transforme into competent R coli cells and chloramphenicol resistant colonies are isolated. 4. Plasmid clones are identified that contain the oligonucleotide from 2. spanning th region from the Nrul site to the BamHI site and recreating these two restriction site This plasmid is termed pREV2.1. Example 3 — Construction of and expression from plasmid pPBl-Sub 1 Plasmid pPBl-Sub 1, which contains approximately 165 base pairs (bp) of DNA encodin essentially the HIV eny gene from the PvuII site to the Dral site, and from which is synthesized a approximately 12 Kd fusion protein containing this portion of the gpl20 envelope protein can constructed as follows: 1. Restricting plasmid pPBl IIIB with Mlul and Dral and isolating the approximately 1 bp fragment. 2. Restricting plasmid pREV2.1 with Mlul and Smal and isolating the large fragment approximately 4 Kd, from an agarose gel. 3. Ligating the fragment prepared in 2. with the pREV2.1 fragment in a volume of 2 μl using T4 DNA Ugase, transforming the ligation mixture into competent cell strai CAG629, and selecting ampicillin-resistant transfoπnants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl2 fragment cloned in the proper orientation to generate a fusion protein. When th strain harboring this recombinant plasmid is grown in 2% medium containing 50μg/ ampicUlin and the total complement of cellular proteins are electrophoresed on SDS-polyacrylamide gel, a protein of approximately 12 Kd can be visualized by eithe coomassie blue staining or by Western blot analysis using as probe selected sera fro HTV infected individuals. Example 4 — Purification of recombinant protein containing HIV envelope sequences from plasmi pPBl-Sub 1 1. Growth of cells: CeUs were grown in a 10-liter volume in a Chemap (Chemape Woodbuiy, NY) fermentor in 2% medium (2% yeast extract, bacto-tryptone, casamin acids pifco, Detroit, MI], 0.2% potassium monobasic, 0.2% potassium dibasic, an 0.2% sodium dibasic). Fermentation temperature was 30°C, the pH was 6.8, and a was provided at 1 wm. Plasmid selection was provided 20 g/ml chloramphenico Typical cell yield (wet weight) was 30 g/1. 2. Cell lysis: 50 g, wet cell weight, of R røli containing the recombinant HIV envelo fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM potassium ethylenediaminetetraacetic acid (KEDTA), 5 mM ditbiothreit (DTT), 15 mM /3-mercaptoethanol, 0.5% TRπ " ON™X-100 (Pharmacia, Piscatawa NJ), and 5 mM phenylmethylsulfonyl fluoride (PMSF). The suspension was incubat for 30 min at room temperature. This material was lysed using a BEAD-BEATER™ (Biospec Product Bartlesville, OK) containing an equal volume of 0.1-0.15 mm glass beads. The lys was done for 6 min at room temperature in 1-min intervals. The liquid was separat from the beads and centrifuged for 2.5 hr at 20,000 xg. The supernatant was remov and the pellet was resuspended in 100 ml 8 M urea, 20 mM Tris-Cl pH 8.0, 5 m DTT, 15 mM /3-mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The pellet w solubilized using a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. 3. CM Chromatography: The dialysate was loaded onto a 100 ml column (2.5 cm x 2 cm) packed with CM FAST FLOW SEPHAROSE™ (Pharmacia) equilibrated in M urea, 10 mM 4-(2-hydroxyethyl-l-piperazine ethane-sulfonic acid (HEPES) pH 6.5 15 mM 3-mercaptoethanol, and 1 mM KEDTA at room temperature. The colum was washed with 200 ml equilibration buffer, and the protein eluted with a 1.0 lite linear gradient from 0-0.4 M NaCl. The HIV protein (12 Kd) eluted at approximatel 0.2 M NaCl as assayed by SDS-polyacrylamide gel electrophoresis. Further purification was obtained by pooling Sub 1-containing fractions an applying to a S-200 (Pharmacia) gel filtration column equilibrated in the same buffe as the previous column. Example 5 — Construction of and expression from plasmid pPBl-Sub 2 Plasmid pPBl-Sub 2, which contains approximately 320 bp of DNA encoding essentially th HTV env gene from the PvuII site to the Seal site, and from which is synthesized an approximatel 18 Kd fusion protein containing this portion of the gpl20 envelope protein, can be constructed a follows: 1. Restricting the pPBlι Iffl plasmid with Mlul and Seal and isolating the approximatel 320 bp fragment. 2. Restricting plasmid pREV2.1 with Mlul and Smal and isolating the large fragmen approximately 4 Kd, from an agarose gel. 3. Ligating the fragment prepared in 2. with the pREV2.1 fragment in a volume of 2 μl using T4 DNA ligase, transforming the ligation mixture into competent cell strai SG20251 and selecting ampicillin-resistant transformants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl2 fragment cloned in the proper orientation to generate a fusion protein. When th strain harboring this recombinant plasmid is grown in 2% medium containing 50/<g ampicillin and the total complement of cellular proteins electrophoresed on an SDS polyacrylamide gel, a protein of approximately 18 Kd can be visualized by eithe coomassie blue staining or by Western blot analysis using as probe selected sera fro HIV infected individuals. Example 6 — Purification of recombinant protein containing HIV envelope sequences from plasmi pPBl-Sub 2 1. Growth of cells: Cells were grown in a 10-liter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 37°C, the pH was 6.8, and air was provide at 1 WE Plasmid selection was provided by 20 g/ml chloramphenicol. Typical cel yield (wet weight) was 30 gfl. 2. Cell lysis: 50 g, wet cell weight, of E. coli containing the recombinant HIV envelop fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA, 5 mM DTT, 15 mM /3-mercaptoethanol, 0.5% TRITON™X 100, and 5 mM PMSF. The suspension incubated for 30 min at room temperatur This material was lysed using a BEAD-BEATER™ containing an equ volume of 0.1-0.15 mm glass beads. The lysis was done for 6 min at roo temperature in 1 min intervals. The liquid was separated from the beads an centrifuged for 2.5 hr at 20,000 xg. The supernatant was removed and the pellet w resuspended in 100 ml 6 M guanidine-hydrochloride, 20 mM Tris-Cl pH 8.0, 5 m DTT, 15 mM β-mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The pellet wa solubiUzed using a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. The supe nate (90 ml) was dialyzed against 4 liters of 8 M urea, 20 m sodium formate, pH 4.0, 1 mM EDTA and 15 mM /3-mercaptoethanol. Dialysis w done each time for 8 hr or longer with three changes of buffer. Spectraphor dialys tubing (S P, McGraw Park, IL) with a 3.5 Kd MW cut-off was used. 3. CM Chromatography: The dialysate was loaded onto a 100 ml column (2.5 cm x 2 cm) packed with CM FAST FLOW SEPHAROSE™ (Pharmacia) equilibrated in M urea, 20 mM sodium formate pH 4.0, 15 mM /3-mercaptoethanol, and 1 mM EDTA at room temperature. The column was washed with 200 ml equilibratio buffer, and the protein eluted with a 1.0 liter linear gradient from 0-0.4 M NaCl. Th HIV protein (18 Kd) eluted at approximately 0.2 M NaCl as assayed by SD polyacrylamide gel electrophoresis. Further purification was obtained by pooling Sub 2-containing fractions an applying to an S-200 (Pharmacia) gel filtration column equilibrated in the same buff as the previous column. Example 7 — Synthetic peptides Synthesis of peptides can be done by a variety of estabUshed procedures, for exampl automated peptide synthesis. Peptides were assembled by soUd-phase synthesis on cross-link polystyrene beads starting from the carboxyl terminus and adding amino acids in a step-wise fashi (Merrifield, R.B. [1963] S. Am. Chem. Soc. 85:2149). Each synthesis was performed on an automat peptide synthesizer (Applied Biosystems 430-A) using standard t-Boc chemistry. Amino acids we coupled as highly reactive symmetric anhydrides formed immediately prior to use. To minimi coupling difficulties, dimethylformamide was used as the coupling buffer. The quantitative ninhydrin assay was used to measure the efficiency of coupling after each amino acid addition (Sarin, V.K., S.B.H. Kent, J.P. Tarn, R.B. Merrifield [1981] Anal. Biochem. 117:147 1981). All peptides were deprotected and cleaved from the polystyrene support using an alternative to HF cleavage. Resin containing peptide was resuspended in a mixture of trifluoroacetic acid, trifluoromethane sulfonic acid, and organic thiol scavengers (Tarn, J.P., W.F. Heath, R.B. Merrifield [1986] J. Am. Chem. Soc 108:5242). Soluble peptide was precipitated with ethyl ether and, after removing ether, resuspended in 200 mM sodium carbonate, 3 M guanidine HC1. The crude peptides were purified by reverse-phase chromatography on a 1.0 cm x 25 cm Vidac semi-preparative C 18 column. The buffers employed were: (A) 0.1% trifluoroacetic acid in H 2 0, and (B) 0.1% trifluoroacetic acid in 80% acetonitrile/20% H 2 0. Gradient elution was utilized to elute the bound peptide and collected fractions were further analyzed to identify pure product. Peptide identity was confirmed by amino acid analysis following 6 N HC1 hydrolysis. The synthesis included the addition of terminal amino acids not homologous to HTV for purposes of labeling, cross-linking, or structure of the peptide. These non-HTV amino acids are indicated in parenthesis. The product of synthesis can be further purified by a number of established separatory techniques, for example, ion exchange chromatography. Example 8 — Construction of and expression from plasmid pPBlpp Plasmid pPBlRp, which contains approximately 565 bp of DNA encoding essentially the HTV RF env gene from the PvuII site to the Bglll site, and from which is synthesized an approximately 27 Kd fusion protein containing this portion of the gpl20 envelope protein can be constructed as follows: 1. Synthesizing DNA fragment in Table 4A 2. Restricting plasmid pREV2.2 with EcoRV and BamHI and isolating the large fragment, approximately 4 Kd, from an agarose gel. 3. Ligating the fragment prepared in 1. with the pREV2.2 fragment in a volume of 20 l using T4 DNA ligase, transforming the ligation mixture into competent cell strain CAG 629, and selecting ampiciUin-resistant transformants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl20 fragment cloned in the proper orientation to generate a fusion protein. When the strain harboring this recombinant plasmid is grown at 32°C in 2% medium containing 50 g/ml ampicillin and the total complement of cellular proteins electrophoresed on an SDS-polyacrylamide gel, a protein of approximately 27 Kd can be visualized by either coomassie blue staining or by Western blot analysis using as probe selected ser from HTV infected individuals. Example 9 - Purification of recombinant protein containing HIV envelope sequences from plasmi E^RF 1. Growth of cells: Cells were grown in a 10-Uter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 30°C, the pH was 6.8, and air was provide at 1 wm. Plasmid selection was provided by 20 g/ml chloramphenicol. Typical cel yield (wet weight) was 30 g/L 2. Cell lysis: 50 g, wet cell weight, of R coli containing the recombinant HIV envelop fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA, 5 mM DDT, 15 mM /3-mercaptoethanol, 0.5% TRITON™X 100, and 5 mM PMSF. 300 mg lysozyme was added and the suspension incubated fo 30 min at room temperature, This material was lysed using a BEAD-BEATER™ containing an equ volume of 0.1-0.15 mm glass beads. The lysis was done for 6 min at roo temperature in 1 min intervals. The liquid was separated from the beads an centrifuged for 2.5 hr at 20,000 xg. The supernatant was removed and the pellet wa resuspended in 100 ml 8 M urea, 20 mM Tris-Cl pH 8.0, 5 mM DTT, 15 mM mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The pellet was solubUized usin a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. The supernate (90 ml) was dialysed against 4 liters of 8 M urea, 20 m HEPES, pH 6.5, 1 mM EDTA and 15 mM /3-mercaptoethanol. Dialysis was don each time for 8 hr or longer with three changes of buffer. Spectrophor dialysis tubin with a 3.5 Kd MW cut-off was used. 3. CM Chromatography: The dialysate was loaded onto a 100 ml column (2.5 cm x 2 cm) packed with CM FAST FLOW SEPHAROSE™ equilibrated in 8 M urea, 1 mM HEPES pH 6.5, 15 mM /3-mercaptoethanol, and 1 mM Na EDTA at roo temperature. The column was washed with 200 ml equiUbrium buffer, and the protei eluted with a 1.0 liter linear gradient from 0-0.4 M NaCl. The HIV protein (26 K eluted at approximately 0.2 M NaCl as assayed by SDS-polyacrylamide g electrophoresis. Further purification was obtained by pooling PBl RF -containing fractions a applying to an S-300 gel filtration column equilibrated in the same buffer as t previous column. Plasmid pPBl MN , which contains approximately 600 bp of DNA encoding essentially the HIVMN env gene from the Bglll site to the Bglll site, and from which is synthesized an approximately 28 Kd fusion protein containing this portion of the gpl20 envelope protein, can be constructed as follows: 1. Synthesizing DNA fragment in Table 5A 2. Restricting plasmid pREV2.2 with BamHI. 3. Ligating the fragment prepared in 1. with the pREV2.2 fragment in a volume of 20 μl using T4 DNA Ugase. transforming the ligation mixture into competent cell strain CAG 629, and selecting ampicillin-resistant transformants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl20 fragment cloned in the proper orientation to generate a fusion protein. When the strain harboring this recombinant plasmid is grown at 32°C in 2% medium containin 50/ig/ml ampicillin and the total complement of cellular proteins electrophoresed on an SDS-polyacrylamide gel, a protein of approximately 28 Kd can be visualized b either coomassie blue staining or by Western blot analysis using as probe selected sera from HTV infected individuals. Example 11 — Purification of recombinant protein containing HTV envelope sequences from plasmi PPB M 1. Growth of cells: Cells were grown in a 10-liter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 30°C, the pH was 6.8, and air was provide at 1 WE Plasmid selection was provided by 20 μg/ml chloramphenicol. Typical cel yield (wet weight) was 30 gf 2. Cell lysis: 50 g, wet cell weight, of R coli containing the recombinant HIV envelop fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA, 5 mM DTT, 15 mM /3-mercaptoethanol, 0.5% TRITON™X 100, and 5 mM PMSF. 300 mg lysozyme was added and the suspension incubated fo 30 min at room temperature. This material was lysed using a BEAD-BEATER™ containing an equa volume of 0.1-0.15 mm glass beads. The lysis was done for 6 min at roo temperature in 1 min intervals. The liquid was separated from the beads an centrifuged for 2.5 hr at 20,000 xg. The supernatant was removed and the pellet wa resuspended in 100 ml 8 M urea, 20 mM Tris-Cl pH 8.0, 5 mM DTT, 15 mM β mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The peUet was solubilized usin a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. The supernate (90 ml) was dialysed against 4 liters of 8 M urea, 20 m HEPES, pH 6.5, 1 mM EDTA, and 15 mM /3-mercaptoethanol. Dialysis was don each time for 8 hr or longer with three changes of buffer. Spectraphor dialysis tubin with a 3.5 Kd MW cut-off was used. 3. CM Chromatography: The dialysate was loaded onto a 100 ml column (2.5 cm x 2 cm) packed with CM FAST FLOW SEPHAROSE™ equilibrated in 8 M urea, 1 mM HEPES pH 6.5, 15 mM /3-mercaptoethanol, and 1 mM KEDTA at roo temperature. The column was washed with 200 ml equilibration buffer, and th protein eluted with a 1.0 Uter linear gradient from 0-0.4 M NaCl. The HIV protei (28 Kd) eluted at approximately 0.2 M NaCl as assayed by SDS-polyacrylamide g electrophoresis. Further purification was obtained by pooling PBl MN -containing fractions an applying to an S-300 gel filtration column equilibrated in the same buffer as th previous column. Example 12 — Construction of and expression from plasmid PBl^ Plasmid pPBl sc , which contains approximately 570 bp of DNA encoding essentially the HIV S env gene from the PvuII site to the Bglll site, and from which is synthesized an approximately 26 fusion protein containing this portion of the gpl20 envelope protein, can be constructed as follow 1. Synthesizing DNA fragment in Table 6A 2. Restricting plasmid pREV2.2 with EcoRV and BamHI and isolating the lar fragment, approximately 4 Kd, from the agarose gel. 3. Ligating the fragment prepared in 1. with the pREV2.2 fragment in a volume of μl using T4 DNA Ugase, transforming the ligation mixture into competent cell stra CAG 629, and selecting ampicillin-resistant transformants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl fragment cloned in the proper orientation to generate a fusion protein. When t strain harboring this recombinant plasmid is grown at 32°C in 2% medium containi 50 μg/ml ampicUHn and the total complement of cellular proteins electrophoresed an SDS-polyacrylamide gel, a protein of approximately 26 Kd can be visualized either coomassie blue staining or by Western blot analysis using as probe selected se from HIV infected individuals. Example 13 — Purification of recombinant protein containing HIV envelope sequences from plasm P p Blsc 1. Growth of cells: Cells were grown in a 10-liter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 30°C, the pH was 6.8, and air was provid at 1 wm. Plasmid selection was provided by 20 /ιg ml chloramphenicol. Typical c yield (wet weight) was 30 g/l. 2. Cell lysis: 50 g, wet cell weight, of R coli containing the recombinant HTV envelo fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA 5 mM DTT, 15 mM /3-mercaptoethanol, 0.5% TRITON™ 100, and 5 mM PMSF. 300 mg lysozyme was added and the suspension incubated f 30 min at room temperature. This material was lysed using a BEAD-BEATER™ containing an equ volume of 0.1-0.15 mm glass beads. The lysis was done for 6 min at roo temperature in 1 min intervals. The liquid was separated from the beads a centrifuged for 2.5 hr at 20,000 xg. The supernatant was removed and the pellet w resuspended in 100 ml 8 M urea, 20 mM Tris-Cl pH 8.0, 5 mM DTT, 15 mM mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The pellet was solubilized usi a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. The supernate (90 ml) was dialysed against 4 liters of 8 M urea, 20 m HEPES, pH 6.5, 1 mM EDTA and 15 mM /3-mercaptoethanol and 1 mM KED at room temperature. The dialysate was loaded onto a 100 ml column (2.5 cm x cm) packed with CM FAST FLOW SEPHAROSE™ equilibrated in 8 M urea, mM HEPES pH 6.5, 15 mM /3-mercaptoethanol, and 1 mM KEDTA at roo temperature. The column was washed with 200 ml equilibration buffer, and t protein eluted with a 1.0 liter linear gradient from 0-0.4 M NaCl. The HIV prote (26 Kd) eluted at approximately 0.2 M NaCl as assayed by SDS-polyacrylamide electrophoresis. Further purification was obtained by pooling PBl S c-∞utaining fractions a applying to an S-300 gel filtration column equilibrated in the same buffer as t previous column. Example 14 — Construction of and expression from plasmid pPBl M1? Plasmid pPBl-w M j--., which contains approximately 560 bp of DNA encoding essentially t HIV* WMI2 SDY gene and from which is synthesized an approximately 26 Kd fusion protein containi this portion of the gpl20 envelope protein, can be constructed as follows: 1. Synthesizing DNA fragment in Table 7A 2. Restricting plasmid pREV2.2 with EcoRV and BamHI and isolating the larg fragment, approximately 4 Kd, from an agarose gel. 3. Ligating the fragment prepared in 1. with the pREV2.2 fragment in a volume of 2 μl using T4 DNA Ugase, transforming the ligation mixture into competent cell strai CAG 629, and selecting ampicillin-resistant transformants. 4. Selecting such transformants, by appropriate restriction patterns, that have the gpl2 fragment cloned in the proper orientation to generate a fusion protein. When th strain harboring this recombinant plasmid is grown at 32°C in 2% medium containin 50 g/ml ampicillin and the total complement of cellular proteins electrophoresed o an SDS-polyacrylamide gel, a protein of approximately 26 Kd can be visualized b either coomassie blue staining or by Western blot analysis using as probe selected ser from HTV infected individuals. Example 15 — Purification of recombinant protein containing HTV envelope sequences from plasmi P p BlwMJ 2 1. Growth of ceHs: Cells were grown in a 10-liter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 30°C, the pH was 6.8, and air was provide at 1 wm. Plasmid selection was provided by 20 g/ml chloramphenicol. Typical cel yield (wet weight) was 30 g I. 2. Cell lysis: 50 g, wet cell weight, of R oαli containing the recombinant HIV envelop fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA 5 mM DTT, 15 mM ^8-mercaptoethanol, 0.5% TRITON™X 100, and 5 mM PMSF. 300 mg lysozyme was added and the suspension incubated fo 30 min at room temperature. This material was lysed using a BEAD-BEATER™ containing an equ volume of 0.1-0.15 mm glass beads. The lysis was done for 6 min at roo temperature in 1 min intervals. The liquid was separated from the beads an centrifuged for 2.5 hr at 20,000 xg. The supernatant was removed and the peUet wa resuspended in 100 ml 8 M urea, 20 mM Tris-Cl pH 8.0, 5 mM DTT, 15 mM mercaptoethanol, 5 mM PMSF, and 1 mM KEDTA The pellet was solubilized usin a polytron homogenizer and centrifuged at 20,000 xg for 2 hr. The supernate (90 ml) was dialysed against 4 Uters of 8 M urea, 20 m HEPES, pH 6.5, 1 mM EDTA and 15 mM /3-mercaptoethanol. Dialysis was don each time for 8 hr or longer with three changes of buffer. Spectraphor dialysis tubi with a 3.5 Kd MW cut-off was used. 3. CM Chromatography: The dialysate was loaded onto a 100 ml column (2.5 cm x cm) packed with CM FAST FLOW SEPHAROSE™ equilibrated in 8 M urea, mM HEPES pH 6.5, 15 mM j8-mercaptoethanol, and 1 mM Na EDTA at roo temperature. The column was washed with 200 ml equilibration buffer, and t protein eluted with a 1.0 liter linear gradient from 0-0.4 M NaCl. The HIV prote (26 Kd) eluted at approximately 0.2 M NaCl as assayed by SDS-polyacrylamide electrophoresis. Further purification was obtained by pooling PBl W M 2 -containing fractio and applying to an S-300 gel filtration column equilibrated in the same buffer as t previous column. Example 16 — Cell fusion inhibition The in vitro fusion of HTV infected ceUs with T4 positive T cells is measured in the presen and absence of immune serum. This is a well known assay (Putney et al. [1986] Science 234:139 1395). Chronically infected cells and uninfected cells (1:15) are mixed and incubated 24 hr. Foci fused cells (giant cells) are then counted (usually about 60). Dilution of an immune serum, example, serum to the entire HTV envelope (gpl60) or to a protein or peptide of the invention, added when the cells are mixed. A 90% decrease in giant cells after 24 hr indicates the immu serum can block fusion. This assay can be done with cells infected with various virus strains, f example, HIV B and HTV R p. Example 17 — Competition cell fusion Using the assay described in Example 16, one can determine if proteins or peptides cont the epitope recognized by antibodies that are responsible for cell fusion inhibition. For examp fusion inhibition of HTVπiβ infected cells by antiserum to the PB1-III B protein of the par application is abated by addition of PB1-III B protein to 5 μgfml. Using antiserum to PB1-III B a adding any one of the proteins or peptides, for example, Sub 2, Sub 1, CNBrl, peptide 135 or pepti 136 at 5 /*g/ml totally blocks the activity of the PB1 antiserum. Additionally, antiserum to PB1- that is capable of neutralizing HTV-RF can be blocked in this activity by peptide 139. A pepti containing only the central portion of the peptide 139, e.g., peptide 339, also can block the fusi inhibition activity of antiserum to PB1-RF. This, for the first time, localizes the critical amino aci necessary to elicit neutralization or block fusion inhibiting antibody to a ten amino acid sequence (e.g., peptide 339). Example 18 - Co-immunization of PBl-IIIp and PBlpp Antisera from an animal immunized with two PB1 proteins from HTV IIIB and HIV RF isolates were capable of blocking cell fusion of both HTVurø- and HTV R p-infected cells. This demonstrates that co-immunization with separate proteins containing envelope sequences of two HIV isolates elicits an immune response capable of neutralizing both isolates. This novel property of small proteins or peptides blocking immune serum has not been described before. Some of the proteins and peptides of the subject invention contain the entire epitope for raising humoral immune responses that neutralize HTV infection and block HIV infected cell fusion. This is shown by these proteins and peptides competing these activities out of serum from animals immunized with the entire HIV envelope. More specifically, proteins and peptides that can compete the activities from anti-gpl60 or anti-PBl sera are Sub 2, Sub 1, CNBrl, peptide 135, and peptide 136. The proteins and peptides of the invention also can be used to stimulate a lymphocyte proliferative response in HIV infected humans. This then would stimulate the immune system to respond to HIV in such individuals. Example 19 — Construction of and expression from plasmid pPBlπm Plasmid pPBl, which contains approximately 540 bp of DNA encoding essentially the HIV env gene from the PvuII site to the Bglll site, and from which is synthesized an approximately 26 Kd fusion protein containing this portion of the gpl20 envelope protein, can be constructed as follows: 1. Synthesizing the DNA with the sequence shown in Table 8: This DNA fragment can be synthesized by standard methods and encodes a portion of gpl20. It has a blunt end on the 5' end and an end which will ligate with a BamHI overhang on the 3' end. 2. Restricting 5 μg plasmid pREV2.2 with EcoRV and BamHI and isolating the larg fragment, approximately 4 Kd, from an agarose gel. 3. Ligating 0.1 μg of the fragment in Table 8 with 0.1 μg of the pREV2.2 fragment i a volume of 20 μl using T4 DNA ligase, transforming the ligation mixture int competent cell strain SG20251, and selecting ampicillin-resistant transformants. 4. Using the Ahalll restriction pattern of purified plasmid, selecting cells harboring th recombinant plasmid with the synthesized fragment in the orientation whereby th fragment blunt end Ugated to the REV2.2 EcoRV end and the BamHI overhangin ends Ugated together. Ahalll digestion of the proper plasmid gives fragment length of approximately 1210, 1020, 750, 690, 500, 340, and 20 base pairs. When the strai harboring this recombinant plasmid is grown in 2% medium containing 50 μg/ ampiciUin and the total complement of cellular proteins electrophoresed on an SD polyaciylamide gel, a protein of approximately 26 Kd can be visualized by eith coomassie blue staining or by Western blot analysis using as probe selected sera fro AIDS, ARC, or HTV infected individuals. Example 20 — Purification of recombinant protein containing HIV envelope sequences from plasmi E BIIIIB 1. Growth of cells: Cells were grown in a 10-liter volume in a Chemap fermentor in 2 medium. Fermentation temperature was 37°C, the pH was 6.8, and air was provide at 1 WE Plasmid selection was provided by 50 μg/aύ ampicillin and 20 g/ chloramphenicol. Typical cell yield (wet weight) was 30 g/1. 2. Cell lysis: 50 g, wet cell weight, of R coli containing the recombinant HIV envelop fusion protein were resuspended in a final volume of 100 ml in 50 mM Tris-Cl p 8.0, 5 mM KEDTA, 5 mM DTT, 15 mM /3-mercaptoethanol, 0.5% TRITON™ 100, and 5 mM PMSF. 300 mg lysozyme was added and the suspension incubated f 30 min at room temperature. This material was lysed using a BEAD-BEATER™ (Biospec. Product Bartlesville, OK) containing an equal volume of 0.1-0.15 mm glass beads. The lys was done for 6 min at room temperature in 1 min intervals. The liquid was separat from the beads and centrifuged for 2.5 hr at 20,000 xg. The supernatant was remov and the pellet was resuspended in 100 ml 6 M guanidine-hydrochloride, 20 mM Tri Cl pH 8.0, 5 mM DTT, 15 mMjS-mercaptoethanol, 5 mM PMSF, and 1 mM KEDT The pellet was solubilized using a polytron homogenizer and centrifuged at 20,0 xg for 2 hr. The supernate (90 ml) was dialysed against 4 liters of 8 M urea, 20 mM Tri Cl, pH 8.0, 1 mM EDTA and 15 mM /3-mercaptoethanol. Dialysis was done ea time for 8 hr or longer with three changes of buffer. Spectraphor dialysis tubing (S/ McGraw Park, IL) with a 3.5 Kd MW cut-off was used. 3. CM Chromatography: The dialysate was loaded onto a 550 ml column (5 cm x cm) packed with CM FAST FLOW SEPHAROSE™ equilibrated in 8 M urea, mM potassium phosphate pH 7.0, 15 mM /3-mercaptoethanol, and 1 mM KEDT at room temperature. The column was washed with 2 liters equilibration buffer, a the protein eluted with a 5.0 liter linear gradient from 0-0.4 M NaCl. The HI protein (26 Kd) eluted at approximately 0.2 M NaCl as assayed by SDS-polyacrylamide gel electrophoresis. Example 21 - Immunization with two or more peptides to obtain broadly neutralizing antisera Five peptides, i.e., peptide 135, peptide 139, peptide 141, peptide 142 and peptide 143, were cross-linked individually to carrier proteins and used to immunize goats. Each peptide is capable o eliciting type specific neutralization when used individually as an immunogen. Synthetic peptides were cross-Unked through a sulfhydiyl bond to keyhole limpet hemocyanin (KLH) by using Succinimidyl 4-(n-Maleimidomethyl)Cyclohexane 1-Carboxylate (Pierce). The ratio of peptide to KLH was 1:2 b weight. 200 μg of each cross-linked peptide was used in the immunization cocktail (a total of 1 m of 5 peptides, 2 mg of KLH). This method of crosslinking or immunization regimen is but an exampl and not meant to be limiting. After four immunizations, immune sera was tested for neutralizatio of these five HTV isolates as well as distinctly different isolates. The immune serum could bloc fusion of cells infected with any of five isolates from which the peptide sequences were derived. I addition, the serum neutralized other variants not used in the immunization. Equivalent broad neutralizing sera may also be obtained by variations of this immunogen. Fo example, using more than five peptides having the amino acid sequence derived from the principa neutralizing domain from more than five variants. Alternatively, a single peptide (e.g., peptide 64 o peptide 74) containing segments homologous to diverse HIV variants may also be used to elicit broa neutralizing antibody. Example 22 — Sequential Immunization with Two or More Peptides as a Method to Elicit Broa Neutralizing Antisera An immunization protocol capable of eliciting broad neutralizing antibodies may take the for of initial immunization with a peptide or protein antigenically equivalent to the principal neutralizin domain, or segments thereof. The initial immunization is followed with a second immunization. Th initial immunization could be done with, for example, peptide 135, peptide 139, peptide 141, peptid 142, or peptide 143, with subsequent immunization with, for example, one or more of the followin peptides: Pro Ala His Cys Asn He S Ser Ala) Gly Pro Gly Arg (Ala Cys) Pro Gin Ala His Cys Asn He S The method is to immunize with a protein or peptide and then boost the immune respons to a defined subset of the original immunogen. This immunization method may be useful in vacci methodology and also to generate broad neutralizing polyclonal or monoclonal antibodies f therapeutic applications. Example 23 — Identification of Critical Segments of the Principal Neutralizing Domain Certain segments of the principal neutralizing domain have been found to be capable eliciting the antigenic and immunogenic responses which are associated with the principal neutralizi domain as a whole. For example, a region of the principal neutralizing domain known as the "tip the loop" has been shown to be capable of raising, and/or binding with, neutralizing antibodies. Th capabUity is observed for the "tip of the loop" of a variety of HTV variants. The tip of the loop comprises a three amino acid segment which is highly conserved betwee HTV variants, together with various amino acids which occur on either side of the three conserv amino acids. The three conserved amino acids, which are Gly Pro Gly, usually occur at, or abou positions 311, 312, and 313 of the HTV envelope protein. The "tip of the loop" comprises the Gly Pro Gly segment together with the 2 to 8 amino aci which flank either or both sides of this segment in any given HTV variant. The amino acids whi flank the conserved segment may be any of the 20 natural amino acids, in any sequential orde Although the amino acid sequence of the principal neutralizing domain varies between different HI 1 isolates, conservation at particular positions, for example at the tip of the loop, suggests that certa amino acids at these positions are necessary for virus function. Example 24 — Sequence of the Principal Neutralizing Determinant from Randomly Selected HIV Isolates Sequences of the principal neutralizing domains (PNDs) from random field isolates we obtained in order to determine the degree of heterogeneity within this region of the envelope protei Peripheral blood lymphocytes (PBLs) from randomly selected HIV-1 infected donors were either c cultured with uninfected PBLs or the virus isolates were adapted to CD4 cell lines. DNA w extracted from these infected cells and a 240 base pair region encoding the PND was amplified polymerase chain reaction using oligonucleotide primers that hybridize with flanking conserved regio This product was cloned into pUC19 and the sequence of the PND from one or more clones fro each original isolate were determined. Because of the heterogeneity of the virus population with one infected individual, when two or more sequences were obtained from one PCR reaction, the sequences sometimes differed. The data obtained from nearly 100 individuals (some infected with a heterogeneous viru population) was evaluated along with previously obtained HTV sequence information. Table 9 list 138 PND sequences from HIV isolates. These sequences indicate that, despite the well-known an frequently dted variabϋity in the amino add sequence of the HTV envelope protein, there is actuall a high degree of conservation in the immunologically critical PND region, particularly in the regio at the center of the PND. Specifically, the Gly-Pro-Gly sequence at the "tip of the loop" occurs i over 90% of the variants. Furthermore, other amino adds at certain positions on each side of the G P-G were also found to be highly conserved. Table 10 shows the frequency of occurrence of th various amino adds at each position in the PND. In addition to the very strong conservation of th glycines flanking the central proline, there is strong conservation at several other positions (e.g., R x 12 , P at x n , G at y π , R at y 14 , and A at y 16 ). A comparison of the relative frequency of variations of a 17-amino acid segment centere about the G-P-G sequence is shown in Table 11. In this table, the sequence which reflects the mo commonly occurring amino acids at each position is Usted first. The dashes indicate identity with th consensus sequence. The remaining sequences are ordered from 2 to 138, according to their homolog to the consensus sequence. Thus, the sequences at the top of the table display the greatest homolo with the consensus sequence. Sequences far down the table display less homology. For example, th amino acid sequences from isolates IIIB and LAV-BRU occur at positions 92 and 93, respectively, o this table. This indicates that these isolates have only limited homology with the consensus sequenc The present research shows that HTV viruses such as IIIB and LAV-BRU having the Gln-Arg (Q- dipeptide to the left of the Gly-Pro-Gly sequence are relatively uncommon. By contrast, the M like sequence in this region (...I H I G P G...) is the most common. The present research sho that prindpal neutralizing domains of other commonly studied variants comprise relatively uncommo sequences. Although the subject invention pertains to the discovery of certain highly conserved regio in the prindpal neutralizing domain, there remains some degree of variability in this region amo the various isolates. This variability includes "missing" or "added" amino acids at certain points in t sequence. Of course, "missing" or "added" amino adds can cause difficulty in devising aesthetical pleasing tables showing the sequences. However, these missing or added amino acids pose no difficul to a person skilled in the art in terms of locating the highly conserved regions which are critical the subject invention. Table 9 shows one representation of 138 PND sequences. Table 11 uses slightly different representation to show the same PND sequences. The primary discussion of sequen conservation can probably best be visualized by reference to the representation shown in Table 1 However, it should be noted that the existence of more than one means for representing the sequences does not compromise the abiUty of the skilled artisan to accurately locate the sequence or the conserved regions. With the discovery of commonly occurring amino add sequences, it is possible, for the firs time, to develop prophylactic and therapeutic compositions which can predictably elicit and/or bin with neutralizing antibodies to a broad range of HTV variants. The generalized formula for such composition can be as follows: a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HTV prindpal neutraUzing domain, a peptide capable of stimulating T-cells, or a general immun stimulant Further analysis of common sequence patterns reveals certain specific patterns which are ver common among HTV isolates. Examples of these common sequences are shown in Table 12 an Figure 1. These common patterns, which are known only as a result of the research and discoverie described here, can be used to make pharmaceutical and diagnostic compositions which can be use with a broad range of HTV isolates. This, of course, can be of critical importance, given the larg number of HIV variants which are now known to exist Table 12 is a compilation of the common sequence patterns that occur in the region at th tip of the loop. For example, approximately 60% of the HTV isolates contain the core sequence I I G P G R (a represents several different residues), approximately 50% contain the sequence I G G R A and approximately 40% contain G P G R A F. When a His residue is present at the position in I a I G P G R, this sequence occurs in approximately 30% of the HIV isolates. A vaccin composition comprising a mixture of peptides having the sequence I a I G P G R where all of th possible replacements for the a are present, is capable of eliciting antibodies which neutralizes majority of HTV variants. Preferably, for use as immunogens, the peptides are linked to carrie proteins or adjuvants as described in Example 21. As shown in Figure 1, common sequence patterns are also apparent within the 17 amino aci segment. Sequences which were isolated 4 or more times are highlighted. These commonly occurrin sequences can be used to formulate vaccine cocktails which elicit a broadly neutralizing response. Fo example, a potential cocktail might contain peptides from each of the eight groups represente Alternatively, the peptide sequences may be presented as a hybrid polypeptide containing the principa neutralizing domain from two or more of these groups. Preferably, such a cocktail will contai peptides which will be capable of raising antibodies which neutralize at least 70% and most preferabl at least 90% of HTV variants. The antigens of the subject invention can be identified by their ability to raise antibodie which bind to certain amino acid sequences. For example, particularly advantageous antigeni compounds would raise antibodies which bind to common amino add sequences such as G-P-G-R A-F, I-G-P-G-R-A-F, I-G-P-G-R-A I-a-I-G-P-G-R, I-a-I-G-P-G-R-A and I-a-I-G-P-G-R-A-F, wher a is any of the 20 amino adds. From Table 10 it can be seen that a polypeptide representing the occurrence of amino acid in all of the variants can be represented as follows: Xl3 Xl2 Xll XlO X9 Xg X 7 X6 5 4 3 2 l G Z G Y2Y3 Y4 YS Y6 Y7 yβ Y9 YlO yil Yl2 Yl3 Yl i5 Yl6 yi7 wherein xj is I, R, M, IQR, V, L, K, F, S, G, Y, SRG, or YQR; x 2 is H, R, Y, T, S, P, F, N, A K, G, or V; x 3 is I, L, M, T, V, E, G, F, or Y; X 4 is R, S, G, H, A, K, or not present; X 5 is K, R, I, N, Q, A TR, RQ, or not present; xe is R, K, S, I, P, Q, E_ G, or T; x 7 is T, K, V, I, A R, P, or E; x 8 is N, NV, Y, KI, I, T, DK, H, or K; x 9 is N, S, K, E, Y, D, I, or Q; x 10 is N, Y, S, D, G, or H; x n is P; x 12 is R, I, or K; Xj 3 is T, I, M or A; z is P, A Q» S, or L; y α is R, K, Q, G, S, or T; y 2 is A V, N, R, K, T, S, F, P, or W; y 3 is F, I, V, L, W, Y, G, S, or T; y 4 is Y, V, H, L, F, S, I, T, M, R, VH, or FT; y 5 is T, A V, Q, H, I, S, Y, or not present; yg is T, R, I, Q, A M, or not present; y 7 is G, E, K, R, T, D, Q, A, H, N, P, or not present; y 8 is R, Q, E, K, D, N, A G, S, I, or not present; y 9 is I, V, R, N, G, or not present; y 10 is I, T, V, K, M, R, L, S, E, Q, A, or not present; yn is G, R, E, K, H, or not present; y 12 is D, N, I, R, T, S, or not present; y 13 is I, M, ME, L, or not present; y 14 is R, G, K, S, E, or not present; y 15 is Q, K, or R; y 16 is A and y 17 is H, Y, R, or Q. Monoclonal and/or polyclonal antibodies with broad neutralizing activity can be generate using the commonly occurring peptide sequences for use in prophylactic or therapeutic compositions The commonly occurring sequences described here can be used in much the same way as the othe peptides described in this application. For example, these peptides can be modified in order t provide T-lymphocyte stimulation, general immune stimulation, to enhance immunogenicity o solubility, or to reduce toxidty. The peptides may also be modified by addition of terminal cystein residue(s) or by conjugation to a carrier protein, adjuvant, spacer, and/or Unker. The peptides ma be fused with other HTV epitopes to produce a multiepitope polypeptide which could be useful wit an even greater number of HTV variants. Also, the peptides can be circularized by bonding betwee cysteine residues. The cysteine residues used to make such drcularized peptides could be the naturall occurring cysteine residues at the ends of the prindpal neutralizing domain, or cysteine residues ma be added to the terminal ends of the peptides. Additionally, vaccine compositions may include peptides containing T helper cell epitopes i combination with protein fragments containing the prindpal neutralizing domain. Several of thes epitopes have been mapped within the HIV envelope, and these regions have been shown to stimulat proliferation and lymphokine release from lymphocytes. Providing both of these epitopes in a vaccin composition may result in the stimulation of both humoral and cellular immune responses. Example 25 — Construction and Cloning of Multi-Epitope Genes Synthetic genes can be constructed which encode proteins comprised of the neutralizin epitopes from more than one HTV isolate. The synthetic gene exemplified here comprises a tande arrangement of DNA sequences encoding neutralizing epitopes from HIV isolates IIIB, RF, SC, M and WMJ1. Each epitope-encoding domain within the gene was designed to encode the 11 amin acids centered at the common Gly-Pro-Gly sequence at the tip-of-the-loop for each of the isolates. Thus, the multi-epitope gene contained 5 different coding regions, each of which encoded a neutralizing epitope from a different isolate. For this particular construction, the epitope which was chosen for each of the 5 isolates consisted of the Gly-Pro-Gly sequence along with the 4 amino acids on either side of the Gly-Pro-Gly sequence from each of the 5 isolates. Domains coding for othe neutralizing epitopes from these isolates could have been incorporated into the multi-epitope gene. Also, genes coding for neutralizing epitopes from other isolates can be used. The genes were constructed such that the domains were linked by DNA sequences encodin four glycine residues. The composition or length of the linking sequence can be varied but preferabl it is a sequence that is non-immunogenic itself. The DNA sequence of the synthetic gene describe here was designed such that restriction sites were encoded at either end of the fragment to facilitat cloning into the vector or, alternatively, to permit the construction of longer multi-epitope genes b attachment of 2 or more shorter genes (Figure 2). In addition, a methionine residue was encoded a the 5' end of the gene to fadUtate cleavage when produced as part of a fusion protein. Figure 3 depicts the steps in the construction of the multi-epitope gene described here. Th amino add sequence encoded by this gene is shown in Table 13. The portions of this amino aci sequence which correspond to each of the 5 isolates are identified in Table 13. Double-stranded subfragments of the full-length gene were first constructed starting wit single-stranded synthetic oUgomers designed to encode tandem neutralizing epitopes and Unking amin add sequences. Any number of subfragments can be used. In this experiment the gene was divide into two portions, but three, four, or more portions can be used. Four single-stranded oligomers o between 67 and 78 nucleotides in length were synthesized (HEO-1, HEO-2, HEO-3, and HEO-4 (Figure 3). The oligomers were designed in pairs (HEO-1 and 2; HEO-3 and 4) as opposite an adjacent strands of the double-stranded subfragments having 10 (HEO-1 + 2) or 11 (HEO-3 +4) base of complementary overlap. The oUgomers of each pair were mixed and heated 65°C for 5 minutes then incubated at 37 °C for 1 hour to anneal. After annealing, the complementary strands of each pair were completed ("filled-in") usin Sequenase (U.S. Biochem) and the four deoxynudeotide triphosphates. This reaction was incubate for 1 hour at room temperature, heated at 65"C for 3 minutes, and then incubated for an addition hour at 37°C with fresh Sequenase. Double-stranded fragments of 141 (HEO-1 +2) and 126 (HEO 3+4) base pairs were generated representing adjacent subfragments of the multi-epitope gene. HEO 1+2 comprised the coding sequences for 3 epitopes plus adjacent linker amino acids; HEO-3 + extended from the fourth epitope to the end of the gene. Following the fill-in reaction, the samples were extracted with phenol/chloroform an precipitated with ethanol by standard procedures. The resulting double-stranded DNAs were digeste with Hindlll (HEO-1 +2) or Sacl (HEO-3+4) and purified on a 3% NuSieve agarose gel. The purified fragments were Ugated with Hindlll + Sacl digested pUC19 (New England Biolabs) in a 3- component ligation and transformed into R coli JM105 cells. The presence of a 256 base pair fragment in pUC19, encoding the full-length multi-epitope gene, was confirmed by restriction analysis and DNA sequencing. The resulting plasmid was designated pUC/MEP-1. The MEP-1 insert was removed from pUC MEP-1 and recloned into Hindlll + Sacl digested pRev2.1 for high-level expression of a fusion protein comprised of a leader portion from the R coli BG gene fused to the multi-epitope protein. The resulting plasmid, designated pMEP-1-8342, was transformed into R ∞U strain SG20251 and the 12.9 Kd multi-epitope fusion protein was identified by coomassie blue staining or Western blot analysis using a probe selected from antisera to the loop- tip peptides from each of the 5 HTV isolates. The fusion protein can be used intact or, alternatively, the leader portion can be cleaved off by cyanogen bromide which cleaves on the carboxy-terminal side of methionine residues. The amino add sequence of the fusion protein is shown in Table 13A The multiepitope peptide can be purified from recombinant cells by methods described above. Other synthetic genes can be constructed which encode tandem neutralizing epitopes from any number of different HTV isolates using the procedure described above. In addition, variations on the above procedure can be made which are meant to be included in the present invention. For example, the lengths of the neutralizing epitopes encoded by a gene can vary, and there can be variation in the length of the individual epitopes within a single gene. Further, the number of neutralizing epitopes within a multi-epitope gene can vary, and the composition or the length of the amino add sequences of the epitopes or the linking sequences can be varied from the example that is described herein. It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and the scope of the appended claims. This work was supported in part under contract number N01-AI-62558, awarded to Repligen Corporation by the National Institute of Allergy and Infectious Diseases (NIAID). gp 120 __W_V/-7/// /// /_W^^^ gp 41 T R P H M N T R K S I R I Q R O P C R A r V T I O K I Q H M R lll B (BH10) - - - - - - - - - S - T K - - - - V I Ϊ A T - Q I - - D I - RF - Y - K - - - - H I - - - Y - T K H I ϊ I - MN - - - - - - - T R 8 - B I - - - - - - Y Λ T - D I - - D I - SC - - - Y V - R S L S I - - - R - R K I I I - WMJ-2 _ _ _ 0 - - - - R β - B r - - - Q - L Y - T - I V - D I - LAV-MAL - - - - - - - - - S - Y I - - - - - - H - T - R I - - D I - SF-2 vθ _ _ _ _ _ _ _ K _ G - A I - - - - T I. Y A R I - I - - » I - NY5 - - - G SDKKI - Q S - R I - - - K V - Y A K - 6 I T - Z3 _ _ _ _. _ _. V - R R B - B I - - - - - - T - 0 K I R - - I - WMJ1 - - - - D I A - R - - B I - - - - - - T - G K I - - - I - WMJ3 - - - Y K - - - Q S T P I - - Q - Y -TRβRT- I - - Z6 A - - Y Q - - - Q - T P I - L - Q 8 Y - TRSRS I - - LAVELI _ _ _ _ _ H - - - - V T L - - - - V H Y - T - K I 1 - - I - CDC451 _ _ _ _ _ _ _ _ _ - V I L - - - - V H Y - T - B I 1 - - I - CDC42 - - - - - - - - - 8 - B I - - - - - - Y - T - B I - - D I - BAL K - - G - K - V - Q - M L M 8 - B V - H S B Y Q PIH K R P - HIV-2 TABLE 2 Leu sr.Glr.SerVslGluIleAsriCysThrAr≤ProAsr.AsriAsriThrAraLys SerlleAr≤IleGlnAr≤GluProGluAr≤AlaPheυalThrlleGlaLysIlE Gly sriMetAr≤GlriAlaHisCyεAsrilleSerAr≤AlaLysTr snABriThr TABLE 2A CTGA CCAATCTGTAG ATT ATTGTACAAGACCCAAC ACA T CAAGA AA AGTATCCGTATCCAGAGAGGACCAGGGAGAGCATTTGTTACAATAGGAAAAATA GGAAATATG B CAAGCACATTGTAACATTAGTAGAGC AAATGG ATAACACTTT TABLE 2B HetLeuAr_3 roValGluThrProThrA*r___GluIleLysLysLeuAspGlyLeu TrpAlaPheSerLeuAspAraGluAraValAla spLeuAsnGlriSerValGlu IleAsnCysThrAr≤PT-o εriAsriAεriThrAr≤LysSerlleAr≤IleGlriAT≤ GlyproGl Ar≤AlsPheVElThrϊleGlyLysIleGlyAsr.MεtArgGlr.Als HiEC 5ABrιIleBerAr≤AlsLy5TrρAsrιAsnThrLeuGlyAlaAτ*≤I leLeu GluAεpGIu r≤AlεSer TABLE 2C ATGTTACGTCCTGTAG ACCCCAACCCGTGAA TCAAAAAACTGGA GGCCTG TGBGCATTCAGTCTGGATCGCGAACGCGTGGCCGATCTG ECA TCTGTAG ATT ATTUT CAAGACCCAACAACAATACAAGAAAAAGTATCCGTATCCAGAGA GG CCAGGGAGAGCATTTGTTAC ATAGGAAAA TAGGAAATATGAGACAAGCA CATTGT CATTAGTAGAGCAAAATGGAATAACACTTTGGGAGCTCG TTCTT B AUMCGA MBGD CTCG TABLE 3 LeuAsr.GlriSerValGluIlεAsriCysThrAr≤ProAsriAsriAsnThrArgLys SεrlleAr≤IleGlnAr≤GlyProGlyAr≤AlaPheValThrlleGlyLysIle GlyAsriMetAr≤GlnAlaHisCysAεrilleSerAr≤AlδLysTrpAsri snThr LeuLysGlnlleAspSerLysLeuAr≤GluGlriPheGlyAεriAsriLysThrll IlεPheLysGlriSerSerGlyGlyAspProGluIleValThrHiεSεrPheAsri CysGl Gl GluPhePheTyrCysAsriSerT rGlnLeuPheAsriSer TABLE 3A CTGAACCAATCTGTAGAAATTAATTGTACAAGACCCAACAACAATACAAGAAAA AGTATCCGTATCCAGAGAGGACCAGGGAGAGCATTTGTTACAATAGGAAAA TA GGAAATATGAGACAAGCACATTGTAACATTAGTAGADCAAAATGGAATAACACT TTAAAACAGATAGATAGCAAATTAAGA6AACAATTTGGAAATA TAAAAC ATA ATCTTTAAGCAGTCCTCAGGAGGGGACCCAGAAATTGTAACGCACAGTTTTA T TGTGGAGGGGAATTTTTCTACTGTAATTCA CACA CTGTTTAATAGT TABLE 3B HetLεuAr≤ProVBlGluThrProThrAr≤GluIleLysLysLεuAεpGlyLεu TrpAlaPheSεrLeuAεpAr≤GluA- ≤ValAlδAspLeuAsriGlriSerVslGlu IleAεrιCysThrAr≤ProAεr.AsnAεnThrAr_3LyεSεrIleAr__SlleGlrιAr≤ Gl ProGlyAr≤AlaPheValThrlleGlyLyεllεGlyAεriMetAr≤GlriAla HiεCysAεnllεSεrAr≤AlsLysTrpAεriAsπThrLεuLyεGlrilleAspSεr LysLεuAr≤GlυGlriPhεGlyAεriAsriLysThrllεllePheLysGlnSerSer GlyGl AspProGluIlευalThrHisSerPheAsriCysGlyGlyGliJPhePhe Ty * rCyεAεr.SerThrGlnLeuPhεAsr.SerGl SerSεrAεrιSer TABLE 3C ATGTTACGTCCTGTAG ACCCCAACCCGTGAAATCAAAAAACTGGACGGCCTG TGDGCATTCAGTCTGGATCGCGAACGCGTGGCCGATCTGAACCAATCTGTAGAA ATTAATTGT C GA 3CAACAACAATACAAGAA A GTATCCGTATCCAGAGA GGACCAGGGAGAGCATTTGTTACAATAGGAAAAATAGGAAATATGAGACAAGCA CATTGTAACF'-TTAGT GAGCAA ATGG ATAACACTTTAAAACAG T G TAGC AA TT AGAG C ATTT6GAAATAATAAAACAATAATCTTTAAGCAGTCCTC GGAGGGGACCCAGAAATTGTAACGCACAGTTTTAATTGTGGAGGGGAATTTTTC TACTGT TTCAA.AC CTGTTTAATAGTGGGAGCTCGAATTCT -i X> CT π H Z ~i x> π cn H 1> H I* r> CT -I 2> CD n π cn tn π 3> -I CT π CT CT CJ T -I 3> -t 3> CT CT -> -i -i ~> CT CT -i __> 2> -i CT CT ~ > CT H .0 X" -I -I CT CT π tn H X« H I> π cn CT CT 3> H CT n H 3> -i _> -I 3> -t -> 3 H -i X> -H 3 -H 2> CT CT H 2> I« -i 3 -I -i 3 ~> H CT CT -I 3> -i -> H X» -H X. cn -i - -I 1- X> H π ci -i ~> CT π π ci 3> -I 3> -i ci -i -> H X* CT CD π tn π cn H X* CT CT ~> -H CT CT 3> -i π CT CT CT CT O π cn ~> -t H 2> CT CT X- -I CT CT -i X» H 2> X* -I -I 3> π n π cj -i _> I- H 3> -H 3> -i CT CT --I _!> -H X ~ ~i π cn π cn X> H CT CT I- -I CT CT I> -H H D* -i x> CT CT 3> -i -i ~> 3> H -I 3> CT CT -H X* ~> H -i ~> CT CT 3> -i π CT cn π CT CT H _t> 2> -I CT CT -I X- O CT n CT CT cn H x H 1 X H -i ~t> H 2> CT CT CT n CT CT CT CT 3> -H - ~ ~> H H X> I> -i CT CT * - 3> H 2> • H 2> H 3 π cn H > H 2 -i 2> 3> H CT CT X> CT CT CT π CT O H I> ~> H H 3> -i 2> CT CT CT CT -I X* -H I> CT CT H 3 2 -i I> H CT π CT CT I * H CT CT H X- I' H H X> -H 3> -i 3> -i ~t> -i 3> -i 3> H I> CT CT 2- -I I> H C J CT H ~t> CT CT -i ~> 3> -I CT n -I 3> -H I> 3> H CT CT CT CT I> H -I .0 H 3> π tn _o *-t X- -i CT π H 2> 3 H CT CT 2 H H 2> ~~ > - ~ f H CT CT -i __ C) CT -t 2> -i ~> -I 2> -i 3> CT π π cn CT CI CT CT CT π CT CT CT CT -i X- CT CT H 3 !• 3 H CT CT H 3> -I 3> -H I> -I ~> CT CT H X» 3> ~i -I I- H CT π CT CT H a CT CT CT CT CT ci X> H -I !*• 2- -i -i _> π C) CT CI -I x H I> X> H X» H O CT W I- —1 -i J> CT CT H I> ~i 3> -I J> H 3> X- H H 3> 3 -H r H I> ~> -i CT CT -I 3> CT C7 -i CT CT H 3> → I> H 3> m C) CI CT CT -H I -I I » H X* !• - I -I t> CT CT I- H CT O tΛ α> -i -i ~t> -I 3> ~Z- -H H 2> X* -I - I I- -I I- H H X> 4 _._. -i 3> -I 2> CT CT CT π C ) CT X- -I 3> X- -H H X» CT CT -i 3> 3> H ~i 3> I -i 3 -I ~> π CT -I CT CD H 3> I- H H _t> CT O π CT H X> X> -i x> X- -i -i X> n CT -i ~> π CT H 3> I * -I CT CT π CT CT CT CT CT CT CT H 3> I> H π CT π 3> -i I- -I H 2> c> π CT rj CT n C I I- -1 • H X- -I I * !• H α> H CT CT -I 3> -t ~> CT O -I -i 3> -I 2> -I X * -I 3 CT C) - I I- CT O -I 3 -I 3 x CT CT -I I» X- H -I I> -i I> -I -I I» CT t ) -i 1> CT -I x> H 3> CT CI X- -I CT CI I- -I • H 3 H I CT n CT CT π CT H 3> H 3> H I> H 3 X» H C ) CT H 3> CT CT CT π CT O π CT CT CT -I I> CT CT CT CT H 3> CT CT -I 2> H 3> 3> H I> -H H X» CT CT H __> CT CT CT CT -i ~> CT π -I 3> 3> H H -t> H I> CT CT -i ~> I- -i 3> H I> -I CT CT 3> -I CT π -I I> -I 3> -I 2> -i ~> π tn CT CT X- -I X * * -I H X» I* -I -i _t> X* H CT π 3> -I CT CT X» H -I I> -I x » -I _!> -I X» H 3> _r> H -i ~> CT CT CT CT -I I* X > -i -I 2> 3> H CT CT -I I J> -i -I X> CT CT I- -i -i -> CT n -I X- H X> 3 -1 CT CT X> -i H 3> T> -i CT CT -i _o -I 3> H 3 3> H CT CT π CT -I I- CT CT I- H CT CT X- CT CD -I ~> cn CT CT CT I- -I I * -i CT CT X> -I H I> -I I> H 3> CT CT H X H 3 CT CT I- -H 3> -i π CT H _0 CT CT CT π π CT CT CT CT I* -I X -I CT CT H I> -I ~> x» -i -I 3> X> H -I _> X> -i -I v -i 3> -I X> TABLE 4B MεtLeuAr≤ProVslGluThrProThrAr≤GluIleLyεLysLeuAspGlyLeu TrpAlaPhεSεrLεijAspAr≤GluAr≤υalAlaAεpLεuAsriAlsSeryalGlri IleAsnCysThrAr≤ProAsriAsnAεnThrAr≤LyεSerlleThrLyεGlyPro GlyAr≤VallleTyrAlaThrGlyGlnllelleGlyAεpIle r≤LyεAlaHiε CyεAεnLBuSer r≤AlaGlnTrpAsriAεriT rLeuLy≥G ' lnValVaϊThrL s LeuAr≤GluGlriPheAεpAεnLysThrlleValPheThrSerSerSerGl Gly AεpF'roGluIlεVslLeuHiεSerPheAεriCyεGl Gl GluPhεPheTyrCyε AsriThrThrGlriLeuF'hε εnSεrThrTrpAεriSerThrGluGl SerAsri εri ThrGlyGlyAεnAεpThrlleThrLeuProCyεAr≤IleLysGlrilleUslAεn HetTrpGlriGluυalGlyLyεAlaMεtTyrAlaPro roIleBerGl Glnlle LyεCyεlleSerAεrilleThrGlyLeuLeijLεuThr T-≤AεpGlyGlyGluAεp ThrThrAsnThrThrGluIleAr≤Ar≤GlriAlsSerAr≤GlυLeuGlυPheLεu LyεThrLyεGlyF'roAr≤ ε ThrProIlePhelleGly TABLE AC ATGTTACGTCCTGTAGAAACCCCAACCCGTGAAATCAAAAAACTG6ACGGCCT6 TGGGCATTCAGTCTGGATCGCGAACGCGTGGCCGATCTGAATGCATCTGTAC A ATT ATTGTACAA6ACCCAACAACAATACAAG AAGTATAACTAAGGGACC GGGAGAGTAATTTATGCAACAGGACAAATAATAOGAG TATAAGA AAGCACAT TGTAACCTTAGTAGAGCACAATGGAATAACACTTTAAAACA6GTAGTTACAAA TTAAGAGAACAATTTGACAATAAAACAATAGTCTTTACGTCATCCTCAGGAGGG GACCCAGAAATTGTACTTCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGT AATACAACACAACTGTTTAATAGTACTTGGAATAGTACTGAAGGGTC ATA C ACTGGAGGAAATGACACAATCACACTCCCATGCAGAATAAAACAAATTGTAAAC ATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGTGGACAAATT AAATGTATATCAAATATTACAGGGCTACTATTAACAAGAGATGGGGGTGAAGAT ACAACTAATACTACAGAGATCCGTCGACAAGCTTCCCGGGAGCTGGAATTCTTG AAGACGAAAGGGCCTC6TGATACTCCTATTTTTATAG6T TABLE 5B MetLeuAr≤ProυalGluThrProThrAr≤GluIleLysLyεLeuAεpGl Leu Tr p AlaPheSεrLeuAs p Ar≤GluAr≤ValAlBAεpIlelleAspGl SerGlu εnPheThrAspAsriAlaLysThrllellεValHiεLeuAεriGluSerValGlri IleAεnCysThrAr≤ProAsriTyrAsriLysAr≤LysAr≤IleHisIleGl Pro GlyAr≤AlaPhεTyrThrThrLysAsrillelleGlyThrlleAr≤GlriAlsHis CyεAεnllεSεrAr≤AlaLyεTrpAεriAε ThrLεϋAr≤DlrillεVεlSεrLyε LεuLyεGluGlnPheLysAsriLyεThrlleυBlPheAsnGlriS rEerGlyGl AεpProGluIlευalMetHisSerPheAεnCysGl Gl GluPhePhεTyrCyε AεriThrSεrProLεuPheAεnSerT rCyεLyεlleLysGlrillelleAεriMet TrpGlriGluValGlyLysAlsMetTyrAlaProProIleGluGlyGlrillεAr-i CyεSerSerAεnlleThrGlyLeuLeuLeuThrAr≤AεpGlyGl LyεAεpThr AspT rAsriAspThrGluIleAr≤Ar≤GlriAlESεrAr≤GluLeuGluPheLeu LyεThrLyεGlyProAr≤AspThrProIlePhelleGly TABLE 5C ATGTTACGTCCTGTAGAAACCCCAACCCGTGAAATCAAAAAACTGGACGGCCTG TGGGCATTCAGTCTGGATCGCGAACGCGTGGCCGATATCATCGATGGATCTGAA AATTTCACAGACAATGCTAAAACCATAATAGTACACCTGAATGAATCTGTACAA ATTAATTGTACAAGACCCAACTACAATAAAAGAAAAAGGATACATATAGGACCA GGGAGAGCATTTTATACAACAAAA TATAATA6GAACTATAAGACAAGCACAT TGTAACATTAGTAGAGCAAAATGGAATGACACTTTAAGACAGATAGTTAGCA A TTAAAAGAACAATTTAAGAATAAAACAATAGTCTTTAATCAATCCTCAGGAGGG 6ACCCAGAAATT6TAATGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGT AATACATCACCACTGTTTAATAGTACTTGCAAAATAAAACAAATTATAAACATG TGGCAGGAAGTAGGAAAAGCAATGTAT6CCCCTCCCATTGAAGGACAAATTAGA TGTTCATCAAATATTACAGGGCTACTATTAACAAGAGAT6GTGGTAAGGACACG. GACACGAACGACACC6AGATCCGTCGACAAGCTTCCCGGGAGCTGGAATTCTTG AAGACGAAAGGGCCTCGTGATACTCCTATTTTTATAGGT TABLE 6B He LeuAr≤ProValGluThrF'roThrAr≤GluIleLysLysLeuAεpGlyLeu Tr p AlaPhεSεrLeuAε p Ar≤GluAr≤ValAlBAs p LεuL y εGluAlaυslGlu IleAsnCyεThrAr≤ProAsriAεriAεriThrThrAr≤SεrlleHiεllεGlyPro GlyAr-aAlaPhεT r laThrGlyAεpIlεlleGlyAεpIle r≤GlriAlaHiε CyεAεrilleSerAr≤AlaLyεTrpAεriAεriThrLeuLysGlrilleUallleLyε LεuAr≤AspGlriPheGluAεriLyεThrll llePheAεri r≤SerSerGlyGly AspProGluIlεValMetHiεSεrPhεAεnCyεGl Gl GluPhεPhεT rCyε AεriSerThrGlriLεijPheSεrSerThrTr εriGlyThrGluGlySerAεriAεri ThrGlyGlyAsriAspThrlleThrLεuProCyεAr≤IleLysGluIlelleAεn MBtTrpGlriGluValGlyLyεAlaMetTyrAlaP-rσFroIleLyεGlyGlr al LyεCyεSerBεrAεnlleThrGlyLεuLeuLeuThr r≤AεpGlyGlyAεriSei- LysAεnGlySerLysAsnThrGluIleAr≤Ar≤GlriAlaSerAr≤GluLεuGlu PheLeuLyεThrLyεGlyProAr≤ ε ThrF-roIlePhεlleGly TABLE 6C ATGTTACGTCCTGTAGAAACCCCAACCCGTGAAATCAAAAAACTGGACGGCCTG TGGGCATTCAGTCTGGATCGCGAACGCGTGGCCGATCTGAAAGAAGCTGTAGAA ATTAATTGTACAAG6CCCAACAACAATACAACAAGAAGTAT CAT TAGGACC GGGAGAGCATTTTATGCAACAGGAGACATAATAGGAGATATAAGACAAGCACAT TGTAACATTAGTAGAGCAAAATGGAATAACACTTTAAAACAGATAGTTATAA TTAAGAGACCAATTTGAGAATAAAACAATAATCTTTAATCGATCCTCAGGAGG GACCCAGAAATTGTAATGCACAGTTTTAATTGTGGAG6GGAATTTTTCTACTGT TTCAACACAACTGTTTAGTAGTACTTGGAATGGTACTGAAGGGTCA T C ACTGGAGGAAATGACACAATCACCCTCCCATGCAGAATAAAAGAAATT TAAAC ATGTGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAAAGGACAAGTT AAATGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTAATAGC AAGAATGGTAGCAAGAATACAGAGATCCGTCGACAAGCTTCCCGGGAGCTGGAA TTCTTGAAGACGAAAGG6CCTCGTGATACTCCTATTTTTAT GGT -4 x> <a i— rπ rπ σ~ -j J to 3 TABLE 7B MetLeuAr_Ξ.ProVslGluThrProThrAr3GluIleLyεLysLεuAsρGlyLe * j Tr p AlaPhεSerLeuAεpAr≤GluArSValAlaAspLeuAsriGluSεrVslGlu IlεAεnCyεThrAr≤ProTyrAsriAsriVBl r≤Ar≤SerLεuSerllεGlypro Gl Ar≤AlaPhe r≤ThrAr≤GluIlelleGl llelleAr≤GlnAlaHisCyε AsnllεSεrAr≤AlaL εTrpAεriAεnThrLeuLyεGlnlleVElGluLyεLeu Ar≤GluGlnPhεLyεAεriLyεThrllευslPheAsnHiεSerSerGlyGl εp ProGluIleVBlThrHisSerF'heAsriCysGl Gl GluPhePhεTyrCyεAεri SεrThrGlriLeuPheAsriSerThrTrpAsriGl ThrAspIleLyεGl AεpAεn LysAsnSerThrLeuIleThrLeuProCysAr≤IleLyεGlrillelleAsnHet TrpGlriGlyVElGlyLasAlsMetTyrAlBProProIleGlriGl GlnlleAra CyεSerSerAsrιIleThr61 LeuLeuLeυThrAr£iAspGl Gl AεrιBeτ5er SεrAr≤GluGluIleArsAr≤GlnAlsSerAr≤GluLeuGluPheLεuLyεThr LyεGl ProAr≤ εpThrProIlePhelleGly 64 TABLE 7C AT6TTACGTCCTGTAGAAACCCCAACCCGTGAAATCAAAAAACTGGACGGCCTG TGGGCATTCAGTCTGGATCGCGAACGCGTGGCCGATCTGAATGAATCTGTAG A ATTAATTGTACAAGACCCTACAACAATGTAAGAAGAAGTCTATCTATAGGACC GGGAGAGCATTTCGTACAAGAGAAATAATAGGAATTATAAGACAAGCACATT6T AACATTAGTAGAGCAAAATGGAATAACACTTTAAAACAGATAGTTGAGA ATTA AGAGAACAATTTAAGAATAAAACAATAGTCTTTAATCATTCCTCAGGAGGGGAC CCAGAAATT6TAACGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAAT TCAACACAACTGTTTAATAGTACTTGGAATGGTACTGACATTAAAGGAGAT AT AAAAATAGCACACTCATCACACTCCCATGCAGAATAAAACAAATTATAAACATG TGGCAGGGAGTAGGCAAAGCAATGTATGCCCCTCCCATCCAAGGACAAATTAGA TGTTCATCAAATATTACAG6GCTGCTATTAACAAGAGATGGTGGTAATAGCAGC AGCAQGGAAGAGATCCGTCGACAAGCTTCCCGGGAGCTGGAATTCTTGAAGACG AAAGGGCCTCGTGATACTCCTATTTTTATAGGT Table 8 5 • CTGAACCAATCTGTAGAAATTAATTGTACAAGACCCAAC GACTTGGTTAGACATCTTTAATTAACATGTTCTGGGTTG AACAATACAAGAAAAAGTATCCGTATCCAGAGAGGACCAGGGAGAGCATTTGTT TTGTTATGTTCTTTTTCATAGGCATAGGTCTCTCCTGGTCCCTCTCGTAAACAA ACAATAGGAAAAATAGGAAATATGAGACAAGCACATTGTAACATTAGTAGAGCA TGTTATCCTTTTTATCCTTTATACTCTGTTCGTGTAACATTGTAATCATCTCGT AAATGGAATAACACTTTAAAACAGATAGATAGCAAATTAAGAGAACAATTTGGA TTTACCTTATTGTGAAATTTTGTCTATCTATCGTTTAATTCTCTTGTTAAACCT AATAATAAAACAATAATCTTTAAGCAGTCCTCAGGAGGGGACCCAGAAATTGTA TTATTATTTTGTTATTAGAAATTCGTCAGGAGTCCTCCCCTGGGTCTTTAACAT ACGCACAGTTTTAATTGTGGAGGGGAATTTTTCTACTGTAATTCAACACAACTG TGCGTGTCAAAATTAACACCTCCCCTTAAAAAGATGACATTAAGTTGTGTTGAC TTTAATAGTACTTGGTTTAATAGTACTTGGAGTACTAAAGGGTCAAATAACACT AAATTATCATGAACCAAATTATCATGAACCTCATGATTTCCCAGTTTATTGTGA GAAGGAAGTGACACAATCACCCTCCCATGCAGAATAAAACAAATTATAAACATG CTTCCTTCACTGTGTTAGTGGGAGGGTACGTCTTATTTTGTTTAATATTTGTAC TGGCAGGAAGTAGGAAAAGCAATGTATGCCCCTCCCATCAGTGGACAAATTAGA ACCGTCCTTCATCCTTTTCGTTACATACGGGGAGGGTAGTCACCTGTTTAATCT TGTTCATCAAATATTACAGGGCTGCTATTAACAAGAGATGGTGGTAATAGCA C ACAAGTAGTTTATAATGTCCCGACGATAATTGTTCTCTACCACCATTATCGT G AATGAGTCCGA 3 ' TTACTCAGGCTCTAG 66 .LKΛ. uruΛnl TTGQVIGRI RQAQC CTRPNYN KRK RIHI GFGRAFY TTKNIIGTI RQAHC CTRPNNN TRR RIKI GFGRAFY TTGQVIGRI RQAQC CTRPNNN TRR .RIHI THGQIIGDI RKAHC CTRFSKT RIKI ATG IAGDL RQAHC CTRFNDI RIHI T GKIIG I RQAHC CTRPNNN RQAHC CTIFNNN TRK '. • rur.__] TTGEIIGDI RQAHC CTRPNNN TRΠ SFGRAFY TTGEIIGDI RQAHC CTRPNNN TRK GFGRAFY TTGEIIGDI RQAHC i_ϊ_ i - - . CTRPMKH TRK GFGRAFY RQAHC EE7-15-3 CTRPNNN TRK SIHI GFGRAFY RQAYC EE7-24-1 CTRPNKN TRK 5IKI GFGRAFY TTGEIIGDI RQAHC CTRPNNN TRK SIHI GFGRAFY ATGAIIGDI RQAHC CTRPNNN TRK SIHI GFGRAFY ATGDIIGDI Ky/in _J * JJ-i TRK GIIII GPGRAFY I.QAHC DD7-1 r~ TRK GIHI GFGRAFY ATGDIIGDI QAHC EE1-330- CIRFNNN TRK GIHI GFGRAΓY RQAHC SC CTRFNNN TTR SIHI GFGRAFY ' im rR*rQ*AϊHC DDlO-1 CTRP NH ' VRRR HIKI GPGRAFY i Jϋ t Ulil J. RQAHC MJ1.5 IRR HIHI GPGRAFY-- GEIRGNI RQAHC KW3-2-2 IRFKNTI RR RIKI GFGRAFS TTRGIQGDI RQAYC DD4-1 TRFYSNV RN RIHI GFGRAFH TTKRITGDM RQARC AFL30-4- TRFYSNV RW RIHI GFGRAFH TTKRITGDM RQARC KW2- 1-1 TRFYSNV RN RIKI GFGRAFH TTKRITGDM RQARC KW2-9-1 TRFYSNV RN RIHI PGRAFH TTKRITGDM RQARC EEG-4-4 TRPYSIJV RN RIHI GFGRAFH TTKRITGDM RQARC EE7-2 0-3 TRFYSNV RN RIKI GPGRAFH TTKRITGDM RQARC R Tf Λ *"ϊ • * * ώ 6 RIRH HI GFGRAFY ATG GMGDI RQAHC KW4-1 3-1 :TRPNNKIPR HFKI GFGRAFY ATGGIEGDI RKARC AF 30 -G-: TRK GIHI GFGRAIY ATGDIIGDI RQAHC K 2-8 ___ TRK GIHI GPGRAVY TTGRIVGDI RQAHC TM5-1 6-1 TRK GIKI TTGRIVGDI RQAHC K 2-8 -1 ARK GIKI RQAHC EE5-6 -1 CTRPDNN ARK GIHI GPGRAVY RQAHC EE6-3 -5 XTRPNNN KK GIHI GPGRA Y TRTRIIGDI RQAHC TK5-8 -1 CTRFNNN TKK GIKI GPGRAVY TARRIIGDI RQAHC TM5-1 2-1 CIRPNIN TGK RIPI GPGRAFY RQAHC EE5-3 _ - «_>_ XTRPNNN TRK SIFI GPGRAFY :GDI RQAHC EE3-2 -4 TRK SIPI GPGRAFY RQAHC H331 XRK SIFI GPGRAFY RQAHC EE1-2 73-1 CTRPNNN TRK GPGRAFY TRQ] VGDI RQAHC EE3-5-1 CMRFNNN TRK GPGRAFY TTGQ IGDI RQAHC WH721 XXXXNNN TRK SINI GPGRAFY ARGEIIGDI RRAXX K 4-3 CTRPNNN TRK 3IAI GPGRAFY ATRRIIGDI RQAHC TM4-1 1-1 CTRPNNN TRK RIYI GPGRAFY ARQQIIGDI RQAHC TM5-13-1 CTRPNNN TRK GFGRAFY ARQQVIGDI RQAHC SF2 CTRPNNN TRK GPGRAFH TTGRIIGDI RKAHC 3F4 CTRPNNN TRK GPGRAFH TTGRIIGDI RKAHC CMRFNNN TRK GPGRAFF ATGDIIGDI RQAHC RR GFGRAFR YRE IGII RQAHC EE6-1- TRK GFGRAFV TTKQIIGDI RQAYC TKK GFGRAVY TTEKIIGDI RRAHC TMi TKK GPGRAVY RRAHC GIRI RQAHC Table 9 (continued) 67 AFL30-11-1 AFL30-12-1 KW4-12-1 KW4-12-2 KW4-7-1 KW4-7-2 K 3-G-1 IIIB (BH10) LAV-BRU EE5-10-1 EE7-3-3 EE7-G-2 KW2-1-3 EE3-G-1 EE7-15-2 EE5-3-1 i: τ .v3* ε- 1 -_.-_. .' -_, l __. CDC 51 Table 9 (continued) 68 KW2- 1-2 EE1- 317- SF170 KW2- 6-2 S3 ΞE3- o-_. 8-1 8-3 TM4- 14-: KW2- 2-1 MAL EE1-317-2 EE1-707-2 SF33 EE7-21-3 TM4-14-3 -e * E7-6-l T3D1-1 AFL30-5-1 ΞΞ7-21-1 TM4-13-2 TM4-13-3 TM3-7-1 AFL30-9-1 kTl.30-9-2 Z6 Table 10 *13 x 12 Xll XlO *9 *8 X 7 X6 X 5 X4 X 3 X 2 X α yi y2 3 4 ys yβ 7 β y9 io n y i2 w yw is iβ yπ Table 11 70 Table 12 COMMON SEQUENCE PATTERNS SE Q UENCE APPROXIMATE OCCURENCE (%. IalGPGR 60 IalGPGRA 50 lalGPGRAF 32 IGPGRA 52 GPGRAF 40 IGPGRAF 35 IGPGR AaY 31 Table 13 IIIB MetThrArglleGlnArgGlyProGlyArgAIaPheVal GlyGlyGlyGly RF SerlleThrArgGlyProGlyArgValHeTyr GlyGlyGlyGly - MN ArglleHisIIeGlyProGlyArgAIaPheTyr GlyGlyGlyGly - SC SerlleHisIIeGIyProGlyArgAlaPheTyr GlyGlyGlyGly - WMJ1 HisIleHisIIeGlyProGlyArgAIaPheTyr GlyGlyGlyGly - LeuSerlleCys Table 13A E.coli BG MetLeuArgProValGluThrProThrArgGluIleLys ysLeuAspGlyLeuTrp - AlaPheSerLeuAspArgGluArgValValArgTyrHisArgTrpIleArgGlnAlaSer IIIB MetThrArglleGlnArgGIyProGlyArgAIaPheVal GlyGlyGlyGly RF SerlleThrArgGlyProGIy r VallleTyr GlyGlyGlyGly - MN ArglleHisIleGIyProGIyArgAlaPheTyr GlyGlyGlyGly - SC SerlleHisIleGlyProGlyArgAlaPheTyr GlyGlyGlyGly - WMJ1 HisIleHisIleGlyProGlyArgAlaPheTyr GlyGlyGlyGly - LeuSerlleCys

Claims: Claims 1. A compound having the capability of eliciting, and/or binding with, neutralizing antibodies whe said capability results from an amino acid sequence which: (a) is the principal neutralizing domain of an HTV variant; (b) is a portion of the principal neutralizing domain of an HIV variant; or (c) is equivalent either to a principal neutralizing domain or a portion thereof. 2. A compound, other than naturally occurring HTV envelope protein, said compound having t capability of eliciting, and/or binding with, neutralizing antibodies, said compound comprising t principal neutralizing domain, or a segment thereof, of an HIV variant. 3. The compound, according to claim 2, wherein said compound is modified by addition of one more of the following moieties: cysteine, a protein or other moiety capable of enhanci immunogenicity, a peptide from an HTV principal neutralizing domain, a peptide capable of stimulati T-cells, or a general immune stimulant. 4. A compound having the capability of eliciting, and/or binding with, neutralizing antibodies, sa compound consisting essentially of the amino acids between cysteine residues occurring at, or arou positions 296 and 331 of the envelope protein of an HIV variant. 5. A compound having the capability of eliciting, and/or binding with, HIV neutralizing antibodi said compound having the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fr an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 6. The compound, according to claim 5, wherein said compound is circularized. 7. The compound, according to claim 5, wherein said compound comprises epitopes from t principal neutralizing domain of more than one HIV variant. 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 and chemical modifications thereof. 1 9. A DNA sequence which codes for a polypeptide, other than the naturally occurring H 2 envelope protein, said polypeptide having the capability of eliciting, and/or binding with, neutraliz 3 antibodies, said polypeptide comprising the principal neutralizing domain, or a segment thereof, of 4 HIV variant 1 10. The DNA sequence, according to claim 9, wherein said polypeptide has the formula 2 a x G z G y b 3 wherein x is 0 to 13 amino acids in length; 4 y is 0 to 17 amino acids in length; and 5 z is P, A, S, Q, or L; and 6 either a or b, but not both, may be omitted; either a or b individually may comprise any one of 7 following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fr 8 an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general imm 9 stimulant. 11. A composition capable of eliciting and/or binding with neutralizing antibodies to a broad ran of HIV variants, said composition comprising one or more compounds having the following formul a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or . and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. y(9) a y_ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y(10) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y l0 y(ll) s y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 y n y(12) a yi y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yι 0 yn y 12 y(13) a yi y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 yn ynyi3 y(14) a yι y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 yn y 1 yi3 yi4 y(15) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yj 0 y n y 12 yi3 yi4 yi5 y(16) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 y n y 12 y χ3 y 14 y 15 y 16 y(17) a y t y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y i0 yn yι 2 yi3yi4 yis yi6 yπ and wherein Xl is I, R, M, IQR, V, L, K, F, S, G, Y, SRG, or YQR; x 2 is H, R, Y, T, S, P, F, N, A, K, G, or V; x 3 is I, L, M, T, V, E, G, F, or Y; 4 is R, S, G, H, A, K, or not present; x 5 is K, R, I, N, Q, A, IR, RQ, or not present; x is R, K, S, I, P, Q, E, G, or T; x 7 is T, K, V, I, A, R, P, or E; x 8 is N, NV, Y, KI, I, T, DK, H, or K; Xg is N, S, K, E, Y, D, I, or Q; xio is N, Y, S, D, G, or H; X H is P; X 2 is R, I, or K; χ 13 is T, I, M or A; yι is R, K, Q, G, S, or T; y 2 is A, V, N, R, K, T, S, F, P, or W; y 3 is F, I, V, L, W, Y, G, S, or T; y 4 is Y, V, H, L, F, S, I, T, M, R, VH, or FT; y s is T, A, V, Q, H, I, S, Y, or not present; y 6 is T, R, I, Q, A, M, or not present; y 7 is G, E, K, R, T, D, Q, A, H, N, P, or not present; y 8 is R, Q, E, K, D, N, A, G, S, I, or not present; y 9 is I, V, R, N, G, or not present; yio is I, T, V, K, M, R, L, S, E, Q, A, or not present; y π is G, R, E, K, H, or not present; y 12 is D, N, I, R, T, S, or not present; y 13 is I, M, ME, L, or not present; y 14 is R, G, K, S, E, or not present; y 7 is G. 17. The composition, according to claim 11, wherein said compound is circularized. 18. The composition, according to claim 11, wherein a and/or b comprise a peptide from an HI principal neutralizing domain. 19. The composition, according to claim 11, wherein said moiety capable of enhancin immunogenicity is a viral particle, microorganism, or immunogenic portion thereof. 20. A prophylactic or therapeutic composition comprising immune globulin, monoclonal antibodies and/or polyclonal antibodies generated by immunizing an appropriate animal such as a mouse, ra horse, goat, human, or chimpanzee with a hybrid compound which comprises compounds where sai polypeptides are not naturally occurring HTV envelope proteins, said polypeptides having the capabilit of eliciting, and/or binding with, neutralizing antibodies, said polypeptides comprising the princip neutralizing domain, or a segment thereof, of an HIV variant 21. A prophylactic or therapeutic composition comprising antibodies generated by immunizing a animal or human with at least one compound comprising a principal neutralizing domain of an HI variant followed by immunization of said animal or human with (a) a mixture comprising compounds, where said compounds are not naturally occurring HI envelope proteins, said compounds having the capability of eliciting, and/or binding wit neutralizing antibodies, said compounds comprising the principal neutralizing domain, a segment thereof, of an HIV variant; or (b) a hybrid compound which comprises polypeptides, where said polypeptides are not naturall occurring HIV envelope proteins, said polypeptides having the capability of eliciting, and/ binding with, neutralizing antibodies, said polypeptides comprising the principal neutralizin domain, or a segment thereof, of an HIV variant 22. A prophylactic or therapeutic composition, comprising an antibody raised against a mixtu comprising compounds, where said compounds are not naturally occurring HIV envelope proteins, b have the capability of eliciting, and/or binding with, neutralizing antibodies, each of said compoun comprising the principal neutralizing domain, or a segment thereof, of an HIV variant. 23. A prophylactic or therapeutic composition, comprising an antibody raised against at least on compound having the capability of eliciting, and/or binding with, HIV neutralizing antibodies, sai compound having the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immun stimulant. 24. The composition, according to claim 23, wherein a and/or b comprises a peptide from an HI principal neutralizing domain. 25. An antibody raised against a compound, said compound having the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immun stimulant. 26. The antibody, according to claim 25, wherein x is selected from x(0) a x is not present x(3) a χ 3 χ 2 χ χ x(4) ≡ X4 x 3 x 2 Xi x(5) a χ 5 χ 4 χ 3 χ 2 χ χ x(6) a xg χ 5 χ 4 χ 3 χ 2 χ χ x(7) a χ 7 xg χ 5 χ 4 χ 3 χ 2 χ χ x(8) a x 8 x 7 xg χ 5 χ 4 χ 3 χ 2 x 1 x(9) a xg χ g χ 7 xg χ 5 χ 4 χ 3 χ 2 χ x(10) ≡ XJO x 9 x 8 x 7 Xg x 5 x 4 x 3 x 2 x-* X(ll) B χ π XJO Xg Xg X 7 g X 5 X 3 X 2 XI x(12) a x 12 x π X i0 Xg Xg x 7 Xg X5 X4 x 3 x 2 x l x(13) a x X3 x 12 x n χ xo Xg x 8 x 7 Xg x 5 X4 x 3 x 2 x 1 z is P, L, A, S, or Q; and y is selected from: y(0) a y is not present y(l) a y x (2) a y x y 2 y(3) a y x y 2 y 3 y(4) a y χ y 2 y 3 y 4 y(5) a y x y 2 y 3 y 4 y 5 y(6) ≡ yι y 2 y 3 y 4 y 5 y 6 y(7) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y(8) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y(9) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y(10) a y x y 2 y 3 y y 5 y 6 y 7 y 8 y 9 yjo y(ll) a yι y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yι 0 yn y(12) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χ0 y χχ y χ2 y(13) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χ0 y xx y x2 y X3 y(14) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χ0 y lχ y χ2 y χ3 y χ4 y(15) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y xo y xα y X2 y x3 y x4 y 15 y(16) a yι y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χo y lχ y 12 y χ3 y χ4 y χ5 y χ6 y(17) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χ0 y xx y X2 y x3 y x4 y x5 y x6 y 17 and wherein x x is I, R, M, IQR, V, L, K, F, S, G, Y, SRG, or YQR; x 2 is H, R, Y, T, S, P, F, N, A, K, G, or V; χ 3 is I, , M, T, V, E, G, F, or Y; χ 4 is R, S, G, H, A, K, or not present; x 5 is K, R, I, N, Q, A, IR, RQ, or not present; g is R, K, S, I, P, Q, E, G, or T; x 7 is T, K, V, I, A, R, P, or E; x 8 is N, NV, Y, KI, I, T, DK, H, or K; χ 9 is N, S, K, E, Y, D, I, or Q; XJO is N, Y, S, D, G, or H; χ χχ is P; χ 12 is R, I, or K χ 13 is T, I, M or A; y χ is R, K, Q, G, S, or T; y 2 is A, V, N, R, K, T, S, F, P, or W; y 3 is F, I, V, L, W, Y, G, S, or T; y 4 is Y, V, H, L, F, S, I, T, M, R, VH, or FT; y 5 is T, A, V, Q, H, I, S, Y, or not present; yg is T, R, I, Q, A, M, or not present; y 7 is G, E, K, R, T, D, Q, A, H, N, P, or not present; y 8 is R, Q, E, K, D, N, A, G, S, I, or not present; yg is I, V, R, N, G, or not present; y X o is I, T, V, K, M, R, L, S, E, Q, A, or not present; yn is G, R, E, K, H, or not present; y x2 is D, N, I, R, T, S, or not present; yι 3 is I, M, ME, L, or not present; y X 4 is R, G, K, S, E, or not present; y i6 is A; and yι 7 is H, Y, R, or Q. 27. The antibody, according to claim 26, wherein said compound(s) are selected from the grou consisting of (a) a-Y-S-N-V-R-N-R-I-H-I-G-P-G-R-A-F-H-T-T-K-R-I-T-b; (b) a-N-N-N-T-S-R-G-I-R-I-G-P-G-R-A-I-L-A-T-E-R-I-I-b; (c) a-N-N-N-T-R-K-G-I-F-I-G-P-G-R-N-I-Y-T-T-G-N-I-I-b; (d) a-N-T-R-K-S-I-R-I-Q-R-G-P-G-R-A-F-V-T-I-G-K-I-G-b; (e) a-N-N-N-T-R-K-R-(I or V)-T-M-G-P-G-R-V-(Y or W)-Y-(X or T)-(A or T)-G-Q-I-I-b; (f) a-N-N-N-(I or T)-R-K-(R or S)-I-T-(R or K)-G-P-G-(R or K)-V-I-Y-A-T-G-Q-I-I-b; (g) a-N-N-N-T-R-K-G-I-Y-V-G-S-G-R-(A or K)-V-T-T-R-(D or H or Q)-K-I-(I or M)-b; an (h) a-T-R-Q-(R or S)-T-P-I-G-L-G-Q-(A or S)-L-Y-T-T-R-b. 28. A vaccine composition for generating a broadly neutralizing immunological response, sai vaccine composition comprising a mixture comprising compounds, where said compounds are n naturally occurring HIV envelope proteins, but have the capability of eliciting, and/or binding wit neutralizing antibodies, said compounds comprising the principal neutralizing domain, or a segme thereof, of HIV variants. 29. A vaccine composition, for generating a broadly neutralizing immunological response, sai vaccine composition comprising a hybrid compound which comprises polypeptides, where sai polypeptides are not naturally occurring HIV envelope proteins, but have the capability of elicitin and/or binding with, neutralizing antibodies, said polypeptides comprising the principal neutralizin domain, or a segment thereof, of an HIV variant 30. A vaccine composition comprising at least one compound having the capability of eliciting and/or binding with, HIV neutralizing antibodies, said compound having the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immun stimulant. 31. The vaccine composition, according to claim 30, wherein said composition is formulated wit an immunological adjuvant. 32. The vaccine, according to claim 30, wherein x is selected from: x(0) a x is not present x(l) a xi x(2) a χ 2 x x x(3) a χ 3 x 2 χ x x(4) a X4 x 3 x 2 χ x x(5) 2 x5 X4 X 3 *2 X l x(6) a xg χ s X4 χ 3 χ 2 χ χ x(7) 3 x 7 X 5 5 X4 X 3 χ 2 χ χ x(8) a χ 8 χ 7 xg χ s , χ 3 χ 2 χ χ x(9) a Xg x 8 x 7 g x 5 x 4 x 3 x 2 x x x(10) a χ xo Xg x 8 x 7 g χ 5 X 4 χ 3 χ 2 χ χ x(ll) a χ xl χ 10 xg x 8 χ 7 xg χ 5 χ 4 χ 3 χ 2 χ χ x(12) a χ 12 χ xx χ xo x 9 x 8 x 7 Xg x 5 x 4 χ 3 x 2 χ x x(13) a χ χ3 χ χ2 χ χχ χ χo Xg x 8 x 7 Xg x 5 ^ χ 3 χ 2 χ χ z is P, L, A, S, or Q; and y is selected from: y(0) a y is not present y(l) a y, y(2) a y χ y 2 y(3) a y χ y 2 y 3 y(5) a y j y 2 y 3 y 4 y 5 y(6) a y j y 2 y 3 y 4 y 5 y 6 y(7) a y x y 2 y 3 y 4 y 5 y 6 y 7 y(8) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y(9) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y(10) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y X o y(ll) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y xo y n y(12) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y x0 y u y 12 y(13) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yι 0 y u y 12 y 13 y(14) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 yn y 12 y X3 y« y(15) a y j y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yι 0 y xl y χ2 y x3 y x4 y x5 y(16) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y x0 yn y 12 yι 3 YuYl5 yi6 y(17) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 y u y 12 y ιs y 14 y 15 y 16 y ιη andwherein xi is I, R, M, IQR, V, L, K, F, S, G, Y, SRG, or YQR; x 2 is H, R, Y, T, S, P, F, N, A, K, G, or V; x 3 is I, L, M, T, V, E, G, F, or Y; x 4 is R, S, G, H, A, K, or not present; ' x 5 is K, R, I, N, Q, A, IR, RQ, or not present; xg is R, K, S, I, P, Q, E, G, or T; x 7 is T, K, V, I, A, R, P, or E; x 8 is N, NV, Y, KI, I, T, DK, H, or K; xg is N, S, K, E, Y, D, I, or Q; xio is N, Y, S, D, G, or H; x xx is P; x X2 is R, I, or K; X l3 is T, I, M or A; yι is R, K, Q, G, S, or T; y 2 is A, V, N, R, K, T, S, F, P, or W; y 3 is F, I, V, L, W, Y, G, S, or T; y 4 is Y, V, H, L, F, S, I, T, M, R, VH, or FT; y 5 is T, A, V, Q, H, I, S, Y, or not present; y 6 is T, R, I, Q, A, M, or not present; y 7 is G, E, K, R, T, D, Q, A, H, N, P, or not present; y 8 is R, Q, E, K, D, N, A, G, S, I, or not present; y 9 is I, V, R, N, G, or not present; yio is I, T, V, K, M, R, L, S, E, Q, A, or not present; yn is G, R, E, K, H, or not present; y x2 is D, N, I, R, T, S, or not present; yis is I, M, ME, L, or not present; yi 4 is R, G, K, S, E, or not present; y 16 is A; and yι 7 is H, Y, R, or Q. 33. The vaccine, according to claim 32, wherein i is T; x 2 is H; x 3 is I; X4 is R; x 5 is K; xg is R; x 7 is T, z is P; y-_ is R; y 2 is A; y 3 is F; y 4 is Y; y 5 is T; y 6 is T; and y 7 is G. 34. The vaccine, according to claim 32, wherein said compound (s) are selected from the gro consisting of (a) a-Y-S-N-V-R-N-R-I-H-I-G-P-G-R-A-F-H-T-T-K-R-I-T-b; (b) a-N-N-N-T-S-R-G-I-R-I-G-P-G-R-A-I-L-A-T-E-R-I-I-b; (c) a-N-N-N-T-R-K-G-I-F-I-G-P-G-R-N-I-Y-T-T-G-N-I-I-b; (d) a-N-T-R-K-S-I-R-I-Q-R-G-P-G-R-A-F-V-T-I-G-K-I-G-b; (e) a-N-N-N-T-R-K-R-(I or V)-T-M-G-P-G-R-V-(Y or W)-Y-(X or T)-(A or T)-G-Q-I-l-b; (f) a-N-N-N-(I or T)-R-K-(R or S)-I-T-(R or K)-G-P-G-(R or K)-V-I-Y-A-T-G-Q-I-I-b; (g) a-N-N-N-T-R-K-G-I-Y-V-G-S-G-R-(A or K)-V-T-T-R-(D or H or Q)-K-I-(l or M)-b; a (h) a-T-R-Q-(R or S)-T-P-I-G-L-G-Q-(A or S)-L-Y-T-T-R-b. 35. The vaccine composition of claim 32 wherein said compound(s) are capable of elicitin antibodies that bind to the sequence G-P-G-R-A-F. 36. The vaccine composition of claim 32 wherein said compound(s) are capable of eliciti antibodies that bind to the sequence I-G-P-G-R-A-F. 37. The vaccine composition of claim 32 wherein said compound(s) are capable of eliciti antibodies that bind to the sequence I-G-P-G-R-A. 38. The vaccine composition of claim 32 wherein said compound(s) are capable of eliciti antibodies that bind to the sequence I-a-I-G-P-G-R. wherein a is any of the 20 amino acids. 39. The vaccine, according to claim 38, wherein a is H. 40. The vaccine composition of claim 32 wherein said compound(s) are capable of eliciti antibodies that bind to the sequence I-a-I-G-P-G-R-A, wherein a is any of the 20 amino acids. 41. The vaccine, according to claim 40, wherein a is H. 42. The vaccine composition of claim 32 wherein said compound(s) are capable of eliciti antibodies that bind to the sequence I-a-I-G-P-G-R-A-F, wherein a is any of the 20 amino acids. 43. The vaccine, according to claim 42, wherein a is H. 44. The vaccine composition, according to claim 30, wherein said compound(s) are circularized. 45. The vaccine composition, according to claim 30, wherein said compound(s) comprise epitop from more than one HIV variant. 46. The vaccine, according to claim 32, wherein Xi is I; z is P; y is R; and y is A. 47. The composition, according to claim 32, wherein χ_ is I; y 3 is F. 49. The vaccine, according to claim 32, wherein x is selected from the group consisting of x(5), x(6 x(7), x(8), x(9), x(10), and x(ll); and y is selected from y(5), y(6), y(7), y(8), y(9), y(10), and y(ll 50. The composition, according to claim 32, wherein said compound has the following amino ac sequence: a-Xι 3 -R-P-Xιo-Xg-X 8 -X 7 -Xg-X 5 -X4-X 3 -X 2 ^^ 51. A kit for use in detecting antibody against HIV in a biological fluid, said kit comprising: (a) a compound, where said compound is not a naturally occurring HIV envelope protein, sa compound having the capability of eliciting, and/or binding with, neutralizing antibodies, sa compound comprising the principal neutralizing domain, or a segment thereof, of an HI variant; and (b) a means for detecting complexes formed between said antibody and said compound. 52. The kit, according to claim 51, wherein said compound has the formula x G z G y wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L. 53. The kit, according to claim 52, wherein x is selected from x(0) a x is not present x(l) a χ χ x(2) a χ 2 χ χ x(3) a χ 3 χ 2 X] x(4) a χ 4 χ 3 χ 2 χ χ x(5) a χ 5 χ 4 χ 3 χ 2 χ χ x(6) a xg x 5 x 4 x 3 x 2 Xj x(7) a χ 7 xg χ s χ 4 x 3 x 2 X j x(8) a x 8 x 7 g χ 5 X4 x 3 x 2 x x x(9) a x 9 x 8 x 7 Xg x 5 x 4 x 3 x 2 Xi x(10) a x 10 x 9 x 8 x 7 Xg x 5 X4 x 3 x 2 Xi x(ll) a xn x x0 x 9 x 8 x 7 Xg x 5 X 4 x 3 x 2 x x x(12) a x x2 xn x xo Xg x 8 x 7 Xg x 5 X 4 x 3 x 2 x 1 x(13) a x χ3 χ 12 χ n Xio Xg x 8 x 7 Xg X5 X4 x 3 X 2 Xi z is P, L, A, S, or Q; and y is selected from: y(0) a y is not present (1) a y x y(2) a y χ y 2 y(3) a y χ y 2 y 3 y(4) a y χ y 2 y 3 y 4 y(5) a y x y 2 y 3 y 4 y 5 y(6) a y x y 2 y 3 y 4 y 5 y 6 y(7) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y(8) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y(9) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y(10) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 10 y(ll) ≡ yi y 2 y 3 y 4 ys ye y7 ys Ys yio y y(12) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 y u y 12 y(13) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 yι 0 y χ ι y n y χ3 y(14) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y x0 y χx y X2 y χ3 y χ4 y(15) a y χ y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y χo y xx y X2 y X3 y X4 y x5 y(16) a y x y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y x0 y X ι y i2 y x3 yi4 Yis Yl6 y(17) a yι y 2 y 3 y 4 y 5 y 6 y 7 y 8 y 9 y 10 yn y 12 y 13 y x4 y x5 y 16 y 17 and wherein x x is I, R, M, IQR, V, L, K, F, S, G, Y, SRG, or YQR; x 2 is H, R, Y, T, S, P, F, N, A, K, G, or V; x 3 is I, L, M, T, V, E, G, F, or Y; x is R, S, G, H, A, K, or not present; x 5 is K, R, I, N, Q, A, IR, RQ, or not present; g is R, K, S, I, P, Q, E, G, or T; x 7 is T, K, V, I, A, R, P, or E; x 8 is N, NV, Y, KI, I, T, DK, H, or K; x 9 is N, S, K, E, Y, D, 1, or Q; xn is P; x ϊ3 is T, I, M or A; y x is R, K, Q, G, S, or T; y 2 is A, V, N, R, K, T, S, F, P, or W; y 3 is F, I, V, L, W, Y, G, S, or T; y 4 is Y, V, H, L, F, S, I, T, M, R, VH, or FT; y 5 is T, A, V, Q, H, I, S, Y, or not present; y 6 is T, R, I, Q, A, M, or not present; y 7 is G, E, K, R, T, D, Q, A, H, N, P, or not present; y 8 is R, Q, E, K, D, N, A, G, S, I, or not present; yg is I, V, R, N, G, or not present; y x0 is I, T, V, K, M, R, L, S, E, Q, A, or not present; y xx is G, R, E, K, H, or not present; y X2 is D, N, I, R, T, S, or not present; y X3 is I, M, ME, L, or not present; y X4 is R, G, K, S, E, or not present; y x5 is Q, K, or R; y x6 is A; and y X7 is H, Y, R, or Q. 54. The kit, according to claim 51, wherein said compound(s) are selected from the group consisti a-Y-S-N-V-R-N-R-I-H-I-G-P-G-R-A-F-H-T-T-K-R-I-T-b; a-N-N-N-T-S-R-G-I-R-I-G-P-G-R-A-I-L-A-T-E-R-I-I-b; a-N-N-N-T-R-K-G-I-F-I-G-P-G-R-N-I-Y-T-T-G-N-I-I-b; a-N-T-R-K-S-I-R-I-Q-R-G-P-G-R-A-F-V-T-I-G-K-I-G-b; a-N-N-N-T-R-K-R-(I or V)-T-M-G-P-G-R-V-(Y or W)-Y-(X or T)-(A or T)-G-Q-I-I-b; a-N-N-N-(I or T)-R-K-(R or S)-I-T-(R or K)-G-P-G-(R or K)-V-I-Y-A-T-G-Q-I-I-b; a-N-N-N-T-R-K-G-I-Y-V-G-S-G-R-(A or K)-V-T-T-R-(D or H or Q)-K-I-(I or M)-b; a (h) a-T-R-Q-(R or S)-T-P-I-G-L-G-Q-(A or S)-L-Y-T-T-R-b. 55. An immunological assay for detecting and/or quantifying antibody against HIV in a fluid, s assay utilizing at least one compound, where said compound is not a naturally occurring HIV envelo protein, said compound having the capability of eliciting, and/or binding with, neutralizing antibodi said compound comprising the principal neutralizing domain, or a segment thereof, of an HIV varia 56. The immunological assay, according to claim 55, wherein said compound has the formula: a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immun stimulant. 57. A method for generating broad neutralizing polyclonal or monoclonal antibodies, said metho comprising immunization with a mixture comprising compounds, where said compounds are n naturally occurring HIV envelope proteins, said compounds having the capability of eliciting, and/ binding with, neutralizing antibodies, where each of said compounds comprises the princip neutralizing domain, or a segment thereof, of an HIV variant. 58. A method for generating broad neutralizing polyclonal or monoclonal antibodies, said metho comprising immunization with a hybrid compound which comprises polypeptides having the capabili of eliciting, and/or binding with, neutralizing antibodies, where each of said polypeptides compris the principal neutralizing domain, or a segment thereof, of an HIV variant. 59. A method for generating broad neutralizing antibodies, said method comprising immunizatio or an animal or human with at least one compound comprising a principal neutralizing domain, segment thereof, of an HIV variant followed by immunization of said animal or human with (a) a mixture comprising compounds, where said compounds are not naturally occurring HI envelope proteins, said compounds having the capability of eliciting, and/or binding wit neutralizing antibodies, said compounds comprising the principal neutralizing domain, a segment thereof, of an HTV variant; or (b) a hybrid compound which comprises polypeptides, where said polypeptides are not natural occurring HIV envelope proteins, said polypeptides having the capability of eliciting, and/ binding with, neutralizing antibodies, said polypeptides comprising the principal neutralizi domain, or a segment thereof, of an HIV variant. 60. A method, according to claim 59, said method comprising immunization with at least on compound having the capability of eliciting, and/or binding with, neutralizing antibodies, sai compound having the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HTV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immun stimulant. 61. A method of detecting antibody against HTV in a biological fluid, comprising the steps of: (a) incubating a compound, other than a naturally occurring HIV envelope protein, sai compound having the capability of eliciting, and/or binding with, neutralizing antibodies, sa compound comprising the principal neutralizing domain, or a segment thereof, of an HI variant; (b) detecting complexes formed between said antibody and said compound. 62. The method, according to claim 61, wherein said compound has the following formula: x G z G y wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L. 63. A method for prophylaxis or treatment of HIV infection, said method comprising administeri to an animal or human in need of such prophylaxis or treatment a composition comprising an antibo raised against a mixture comprising compounds, where said compounds are not naturally occurri HIV envelope proteins, but have the capability of eliciting, and/or binding with, neutralizing antibodi each of said compounds comprising the principal neutralizing domain, or a segment thereof, of an HI variant. 64. The method, according to claim 63, wherein said compounds have the following formula: a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of th following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 65. A method for stimulating a lymphocyte proliferative response in humans which compris treating humans in need of stimulation of a lymphocyte proliferative response with at least o compound, said compound is not a naturally occurring HIV envelope protein, said compound havi the capability of eliciting, and/or binding with, neutralizing antibodies, said compound comprising t principal neutralizing domain, or a segment thereof, of an HIV variant 66. The method, according to claim 65, wherein said compound has the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or l ~ and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 67. A method for treatment of HTV infection, said method comprising administering to an anim or human in need of such treatment a composition comprising one or more compounds wherein sa compounds are not naturally occurring HIV envelope proteins, but have the capability of elicitin and/or binding with, neutralizing antibodies, each of said compounds comprising the princip neutralizing domain, or a segment thereof, of an HIV variant. 68. The method, according to claim 67, wherein said compounds have the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 69. A method for assaying a biological fluid for the presence of an HIV variant-specific protei said method comprising (a) contacting said fluid with an antibody specific for compounds wherein said compounds ar not naturally occurring HIV envelope proteins, but have the capability of eliciting, and/ binding with, neutralizing antibodies, said compounds comprising the principal neutralizin domain, or a segment thereof, of an HIV variant; and (b) detecting immune complexes as a measure of said variant in said fluid. 70. The method, according to claim 69, wherein said compounds of part (c) have the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant 71. A method of in vitro lymphocyte stimulation comprising treating lymphoid cells from immu animals with at least one compound, other than naturally occurring HIV envelope proteins, sa compound having the capability of eliciting, and/or binding with, neutralizing antibodies, sa compound comprising the principal neutralizing domain, or a segment thereof, of an HIV variant. 72. The method, according to claim 71, where said compound has the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or L; and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HIV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 73. A method of identifying polyclonal or monoclonal antibodies which are useful in prophyla or therapy, said method comprising screening antibody-producing cells for ability to bind with at le one compound, other than naturally occurring HIV envelope proteins, said compound having t capability of eliciting, and/or binding with, neutralizing antibodies, said compound comprising t principal neutralizing domain, or a segment thereof, of an HIV variant. 74. The method, according to claim 73, wherein said compound has the formula a x G z G y b wherein x is 0 to 13 amino acids in length; y is 0 to 17 amino acids in length; and z is P, A, S, Q, or l_ and either a or b, but not both, may be omitted; either a or b individually may comprise any one of t following: cysteine, a protein or other moiety capable of enhancing immunogenicity, a peptide fro an HTV principal neutralizing domain, a peptide capable of stimulating T-cells, or a general immu stimulant. 75. A synthetic gene which encodes for a polypeptide wherein said polypeptide comprises more th one HIV neutralizing epitope. 76. A synthetic gene which codes for a polypeptide wherein said polypeptide comprises neutralizi epitopes from more than one HIV isolate. 77. The synthetic gene, according to claim 76, wherein said polypeptide comprises neutralizi epitopes from 2 to 20 HTV isolates. 78. The synthetic gene, according to claim 76, wherein one of said neutralizing epitopes is fr the HIV isolate designated HIV-MN. 79. The synthetic gene, according to claim 76, wherein said polypeptide comprises neutralizi epitopes from the HIV isolates which have been designated HIV-MN, HIV-IIIB, HIV-RF, HIV- and HIV-WMJ1. 80. The synthetic gene, according to claim 76, wherein the regions encoding neutralizing epito from different HIV isolates are separated by amino acid spacers. 81. The synthetic gene, according to claim 80, wherein said amino acid spacers are glycines. 82. The synthetic gene, according to claim 76, wherein said gene codes for a polypeptide havi the amino acid sequence shown in Table 13, or an equivalent amino acid sequence. 83. The synthetic gene, according to claim 76, wherein said gene codes for a fusion polypeptide. 84. The synthetic gene, according to claim 83, wherein said gene codes for a polypeptide havi the amino acid sequence shown in Table 13A, or an equivalent amino acid sequence. 85. A compound comprising neutralizing epitopes from more than one HIV isolate. 86. The compound, according to claim 85, wherein said compound comprises neutralizing epitop from 2 to 20 HIV isolates. 87. The compound, according to claim 85, wherein one of said neutralizing epitopes is from t HIV isolate designated HIV-MN. 88. The compound, according to claim 85, wherein said compound comprises neutralizing epitop from the HIV isolates which have been designated HIV-MN, HTV-IIIB, HIV-RF, HIV-SC, and HI WMJ1. 89. The compound, according to claim 85, wherein said neutralizing epitopes are separated amino acid spacers. 90. The compound, according to claim 89, wherein said amino acid spacers are glycines. 91. The compound, according to claim 85, wherein said compound has the amino acid sequen shown in Table 13, or an equivalent amino acid sequence. 92. The compound, according to claim 85, wherein said compound is a fusion polypeptide. 93. The compound, according to claim 92, wherein said compound has the amino acid sequen shown in Table 13A, or an equivalent amino acid sequence. 94. A prophylactic or therapeutic composition, comprising immune globulin, monoclonal antibodi and/or polyclonal antibodies generated by immunizing an appropriate animal with a compositi comprising a multi-epitope compound wherein said multi-epitope compound comprises neutralizi epitopes from 2 to 20 HIV isolates, wherein one of said isolates is HIV-MN. 95. The composition, according to claim 94, wherein said multi-epitope compound compri neutralizing epitopes from the HIV isolates designated HIV-MN, HIV-IIIB, HIV-RF, HIV-SC, a HIV-WMJ1. 96. A method for generating broad neutralizing polyclonal or monoclonal antibodies, said meth comprising immunizing an appropriate animal with a composition comprising a multi-epito compound wherein said multi-epitope compound comprises neutralizing epitopes from 2 to 20 H isolates, wherein one of said isolates is HIV-MN. 97. The method, according to claim 96, wherein said multi-epitope compound comprises neutralizi epitopes from the HIV isolates which have been designated HIV-MN, HIV-IIIB, HIV-RF, HIV- and HIV-WMJ1. 98. A method for prophylaxis or therapy of HIV infection, said method comprising administeri to an animal or human in need of such prophylaxis or therapy a pharmaceutical compositi comprising immune globulin, monoclonal antibodies, and/or polyclonal antibodies generated immunizing an appropriate animal with a composition comprising a multi-epitope compound wher said compound comprises neutralizing epitopes from 2 to 20 HIV isolates, wherein one of said isola is HIV-MN. 99. The method, according to claim 98, wherein said multi-epitope compound comprises neutralizi domains from the HIV isolates which have been designated HIV-MN, HIV-IIIB, HIV-RF, HIV- and HIV-WMJ1. 100. A process for stimulating a lymphocyte proliferative response in humans which compri treating humans in need of stimulation of a lymphocyte proliferative response with a compositi comprising a multi-epitope compound wherein said compound comprises a neutralizing domain fr 2 to 20 HTV isolates, wherein one of said isolates is HIV-MN. 101. The process, according to claim 100, wherein said multi-epitope compound compri neutralizing epitopes from the HIV isolates which have been designated HIV-MN, HIV-IIIB, HI RF, HIV-SC, and HIV-WMJ1.

Inventors: FARLEY JOHN, GRIMAILA RAYMOND, JAVAHERIAN KASHAYAR, LAROSA GREGORY, LYNN DEBRA, O'KEEFFE THOMAS, PETRO-BREYER JOAN, PROFY ALBERT T, PUTNEY SCOTT D, RUSCHE JAMES R, FARLEY, JOHN, GRIMAILA, RAYMOND, JAVAHERIAN, KASHAYAR, LAROSA, GREGORY, LYNN, DEBRA, O'KEEFFE, THOMAS, PETRO-BREYER, JOAN, PROFY, ALBERT, T., PUTNEY, SCOTT, D., RUSCHE, JAMES, R.
Applicants: REPLIGEN CORP, REPLIGEN CORPORATION
Application year: 1989
Main classification: C07K7
IPC codes: A61K38, A61K39, A61K49, C07K5, C07K7, C07K14, C07K16, C07K19, C12N15, C12P21, C12R1, G01N33