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. 1986 Nov;5(11):3065–3071. doi: 10.1002/j.1460-2075.1986.tb04607.x

Induction of anti-HIV neutralizing antibodies by synthetic peptides.

T C Chanh, G R Dreesman, P Kanda, G P Linette, J T Sparrow, D D Ho, R C Kennedy
PMCID: PMC1167262  PMID: 3466790

Abstract

Two synthetic peptides containing amino acid sequences analogous to the envelope glycoprotein of human T-lymphotropic virus (HTLV) type III (HTLV-III) and lymphadenopathy associated virus (LAV) were produced and used to immunize rabbits. The subsequent rabbit antisera neutralized HTLV-III infectivity in vitro. The two synthetic peptides corresponded to regions associated with the gp120 or gp41 subunits respectively, of human immunodeficiency virus (HIV). This data indicates that at least two neutralizing epitopes are present on the envelope glycoprotein of HIV and these epitopes are associated with two distinct virus envelope glycoproteins. Antisera generated against these peptides neutralized infectivity of two different isolates of HTLV-III. The data is discussed in terms of possible strategy for developing an effective vaccine against the etiologic agents of acquired immune deficiency syndrome (AIDS).

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Selected References

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  1. ANDERER F. A., SCHLUMBERGER H. D. PROPERTIES OF DIFFERENT ARTIFICIAL ANTIGENS IMMUNOLOGICALLY RELATED TO TOBACCO MOSAIC VIRUS. Biochim Biophys Acta. 1965 Mar 8;97:503–509. doi: 10.1016/0304-4165(65)90163-7. [DOI] [PubMed] [Google Scholar]
  2. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
  3. Alter H. J., Eichberg J. W., Masur H., Saxinger W. C., Gallo R., Macher A. M., Lane H. C., Fauci A. S. Transmission of HTLV-III infection from human plasma to chimpanzees: an animal model for AIDS. Science. 1984 Nov 2;226(4674):549–552. doi: 10.1126/science.6093251. [DOI] [PubMed] [Google Scholar]
  4. Anderer F. A., Schlumberger H. D. Cross-reactions of antisera against the terminal amino acid and dipeptide of tobacco mosaic virus. Biochim Biophys Acta. 1966 Jan 25;115(1):222–224. doi: 10.1016/0304-4165(66)90067-5. [DOI] [PubMed] [Google Scholar]
  5. Arnon R., Shapira M., Jacob C. O. Synthetic vaccines. J Immunol Methods. 1983 Jul 29;61(3):261–273. doi: 10.1016/0022-1759(83)90220-x. [DOI] [PubMed] [Google Scholar]
  6. Barin F., McLane M. F., Allan J. S., Lee T. H., Groopman J. E., Essex M. Virus envelope protein of HTLV-III represents major target antigen for antibodies in AIDS patients. Science. 1985 May 31;228(4703):1094–1096. doi: 10.1126/science.2986291. [DOI] [PubMed] [Google Scholar]
  7. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  8. Benn S., Rutledge R., Folks T., Gold J., Baker L., McCormick J., Feorino P., Piot P., Quinn T., Martin M. Genomic heterogeneity of AIDS retroviral isolates from North America and Zaire. Science. 1985 Nov 22;230(4728):949–951. doi: 10.1126/science.2997922. [DOI] [PubMed] [Google Scholar]
  9. Bhatnagar P. K., Mao S. J., Gotto A. M., Jr, Sparrow J. T. The application of an improved solid phase synthetic technique to the delineation of an antigenic site of apolipoprotein A-II. Peptides. 1983 May-Jun;4(3):343–349. doi: 10.1016/0196-9781(83)90145-6. [DOI] [PubMed] [Google Scholar]
  10. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. doi: 10.1038/298030a0. [DOI] [PubMed] [Google Scholar]
  11. Clavel F., Klatzmann D., Montagnier L. Deficient LAV1 neutralising capacity of sera from patients with AIDS or related syndromes. Lancet. 1985 Apr 13;1(8433):879–880. doi: 10.1016/s0140-6736(85)92243-3. [DOI] [PubMed] [Google Scholar]
  12. Dreesman G. R., Benyesh-Melnick M. Spectrum of human cytomegalovirus complement-fixing antigens. J Immunol. 1967 Dec;99(6):1106–1114. [PubMed] [Google Scholar]
  13. Emini E. A., Jameson B. A., Wimmer E. Priming for and induction of anti-poliovirus neutralizing antibodies by synthetic peptides. Nature. 1983 Aug 25;304(5928):699–703. doi: 10.1038/304699a0. [DOI] [PubMed] [Google Scholar]
  14. Fearney F. J., Leung C. Y., Young J. D., Benjamini E. The specificity of antibodies to a peptide determinant of the tobacco mosaic virus protein induced by immunization with the peptide conjugate. Biochim Biophys Acta. 1971 Sep 28;243(3):509–514. doi: 10.1016/0005-2795(71)90024-9. [DOI] [PubMed] [Google Scholar]
  15. Fischinger P. J., Robey W. G., Koprowski H., Gallo R. C., Bolognesi D. P. Current status and strategies for vaccines against diseases induced by human T-cell lymphotropic retroviruses (HTLV-I, -II, -III). Cancer Res. 1985 Sep;45(9 Suppl):4694s–4699s. [PubMed] [Google Scholar]
  16. Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Francis D. P., Feorino P. M., Broderson J. R., McClure H. M., Getchell J. P., McGrath C. R., Swenson B., McDougal J. S., Palmer E. L., Harrison A. K. Infection of chimpanzees with lymphadenopathy-associated virus. Lancet. 1984 Dec 1;2(8414):1276–1277. doi: 10.1016/s0140-6736(84)92824-1. [DOI] [PubMed] [Google Scholar]
  18. Francis D. P., Petricciani J. C. The prospects for and pathways toward a vaccine for AIDS. N Engl J Med. 1985 Dec 19;313(25):1586–1590. doi: 10.1056/NEJM198512193132506. [DOI] [PubMed] [Google Scholar]
  19. Fultz P. N., McClure H. M., Swenson R. B., McGrath C. R., Brodie A., Getchell J. P., Jensen F. C., Anderson D. C., Broderson J. R., Francis D. P. Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome. J Virol. 1986 Apr;58(1):116–124. doi: 10.1128/jvi.58.1.116-124.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gajdusek D. C., Amyx H. L., Gibbs C. J., Jr, Asher D. M., Rodgers-Johnson P., Epstein L. G., Sarin P. S., Gallo R. C., Maluish A., Arthur L. O. Infection of chimpanzees by human T-lymphotropic retroviruses in brain and other tissues from AIDS patients. Lancet. 1985 Jan 5;1(8419):55–56. doi: 10.1016/s0140-6736(85)91011-6. [DOI] [PubMed] [Google Scholar]
  21. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  22. Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
  23. Ho D. D., Rota T. R., Hirsch M. S. Antibody to lymphadenopathy-associated virus in AIDS. N Engl J Med. 1985 Mar 7;312(10):649–650. doi: 10.1056/NEJM198503073121015. [DOI] [PubMed] [Google Scholar]
  24. Ho D. D., Rota T. R., Hirsch M. S. Infection of human endothelial cells by human T-lymphotropic virus type I. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7588–7590. doi: 10.1073/pnas.81.23.7588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kennedy R. C., Henkel R. D., Pauletti D., Allan J. S., Lee T. H., Essex M., Dreesman G. R. Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein. Science. 1986 Mar 28;231(4745):1556–1559. doi: 10.1126/science.3006246. [DOI] [PubMed] [Google Scholar]
  27. Levy J. A., Hoffman A. D., Kramer S. M., Landis J. A., Shimabukuro J. M., Oshiro L. S. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science. 1984 Aug 24;225(4664):840–842. doi: 10.1126/science.6206563. [DOI] [PubMed] [Google Scholar]
  28. Masur H., Michelis M. A., Greene J. B., Onorato I., Stouwe R. A., Holzman R. S., Wormser G., Brettman L., Lange M., Murray H. W. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. 1981 Dec 10;305(24):1431–1438. doi: 10.1056/NEJM198112103052402. [DOI] [PubMed] [Google Scholar]
  29. McDougal J. S., Cort S. P., Kennedy M. S., Cabridilla C. D., Feorino P. M., Francis D. P., Hicks D., Kalyanaraman V. S., Martin L. S. Immunoassay for the detection and quantitation of infectious human retrovirus, lymphadenopathy-associated virus (LAV). J Immunol Methods. 1985 Jan 21;76(1):171–183. doi: 10.1016/0022-1759(85)90489-2. [DOI] [PubMed] [Google Scholar]
  30. Montagnier L., Clavel F., Krust B., Chamaret S., Rey F., Barré-Sinoussi F., Chermann J. C. Identification and antigenicity of the major envelope glycoprotein of lymphadenopathy-associated virus. Virology. 1985 Jul 15;144(1):283–289. doi: 10.1016/0042-6822(85)90326-5. [DOI] [PubMed] [Google Scholar]
  31. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
  32. Pauletti D., Simmonds R., Dreesman G. R., Kennedy R. C. Application of a modified computer algorithm in determining potential antigenic determinants associated with the AIDS virus glycoprotein. Anal Biochem. 1985 Dec;151(2):540–546. doi: 10.1016/0003-2697(85)90217-9. [DOI] [PubMed] [Google Scholar]
  33. Pfaff E., Mussgay M., Böhm H. O., Schulz G. E., Schaller H. Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus. EMBO J. 1982;1(7):869–874. doi: 10.1002/j.1460-2075.1982.tb01262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  35. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  36. Robert-Guroff M., Brown M., Gallo R. C. HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex. Nature. 1985 Jul 4;316(6023):72–74. doi: 10.1038/316072a0. [DOI] [PubMed] [Google Scholar]
  37. Robey W. G., Safai B., Oroszlan S., Arthur L. O., Gonda M. A., Gallo R. C., Fischinger P. J. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985 May 3;228(4699):593–595. doi: 10.1126/science.2984774. [DOI] [PubMed] [Google Scholar]
  38. Sanchez-Pescador R., Power M. D., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., Renard A., Randolph A., Levy J. A. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484–492. doi: 10.1126/science.2578227. [DOI] [PubMed] [Google Scholar]
  39. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  40. Siegal F. P., Lopez C., Hammer G. S., Brown A. E., Kornfeld S. J., Gold J., Hassett J., Hirschman S. Z., Cunningham-Rundles C., Adelsberg B. R. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981 Dec 10;305(24):1439–1444. doi: 10.1056/NEJM198112103052403. [DOI] [PubMed] [Google Scholar]
  41. Smith C. W., Skala G., Wilks J. W. Synthesis of [1, 6-cyclo (acetyl-1-L-glutamic acid, 2-D-phenylalanine, 3-D-tryptophan, 6-D-lysine)] luteinizing hormone-releasing hormone on poly-N-acrylylpyrrolidine resin. Int J Pept Protein Res. 1983 Feb;21(2):127–134. doi: 10.1111/j.1399-3011.1983.tb03086.x. [DOI] [PubMed] [Google Scholar]
  42. Sparrow J. T. An improved polystyrene support for solid phase peptide synthesis. J Org Chem. 1976 Apr 16;41(8):1350–1353. doi: 10.1021/jo00870a013. [DOI] [PubMed] [Google Scholar]
  43. Sutcliffe J. G., Shinnick T. M., Green N., Lerner R. A. Antibodies that react with predetermined sites on proteins. Science. 1983 Feb 11;219(4585):660–666. doi: 10.1126/science.6186024. [DOI] [PubMed] [Google Scholar]
  44. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  45. Weiss R. A., Clapham P. R., Cheingsong-Popov R., Dalgleish A. G., Carne C. A., Weller I. V., Tedder R. S. Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature. 1985 Jul 4;316(6023):69–72. doi: 10.1038/316069a0. [DOI] [PubMed] [Google Scholar]
  46. Wong-Staal F., Gallo R. C. Human T-lymphotropic retroviruses. Nature. 1985 Oct 3;317(6036):395–403. doi: 10.1038/317395a0. [DOI] [PubMed] [Google Scholar]
  47. Zagury D., Bernard J., Leonard R., Cheynier R., Feldman M., Sarin P. S., Gallo R. C. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986 Feb 21;231(4740):850–853. doi: 10.1126/science.2418502. [DOI] [PubMed] [Google Scholar]

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