1887

Abstract

An analysis of the humoral immunogenicity of a candidate AIDS vaccine (VaxSyn) in a murine model system is presented. Sera taken from a panel of mice immunized with the immunogen were analysed for their ability to bind a panel of gpl20-representing peptides and limited reactivity to known sites of immunological interest was observed. Monoclonal antibodies (MAbs) were characterized as binding to a more restricted variety of regions on gpl20 including Cl, V2, V4 and the C terminus. A tetrazolium-based cytocidicity assay was used and shown to be an effective and objective method for the screening of human immunodeficiency virus (HlV)-neutralizing activity in large numbers of samples. None of the MAbs characterized in this study neutralize HIV-1 reference strains. The significance of these findings in view of previous publications is discussed.

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1994-08-01
2024-04-19
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References

  1. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Fiershberg R. D., Cobb E. K., Eichberg J. W. 1990; Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gpl20 but not gp160. Nature; London: 345622–625
    [Google Scholar]
  2. Bonner W. M., Laskey R. A. 1974; A film detection method for tritium-labeled proteins and nucleic acids in polyacrylamide gels. European Journal of Biochemistry 46:83–88
    [Google Scholar]
  3. Dalgleish A. G., Beverly P. C. L., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. 1984; The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature; London: 312763–767
    [Google Scholar]
  4. Drake J. W. 1993; Rates of spontaneous mutation among RNA viruses. Proceedings of the National Academy of Sciences, U.S.A 90:4171–4175
    [Google Scholar]
  5. Fazekas de St Groth S., Scheidegger D. 1980; Production of monoclonal antibodies: strategy and tactics. Journal of Immunological Methods 35:1–21
    [Google Scholar]
  6. Foley G. E., Lazarus H., Farber S., Uzman B. G., Boone B. A., Mccarthy R. E. 1965; Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia. Cancer 18:522–529
    [Google Scholar]
  7. Folks T. M., Powell D., Lightfoote M., Koenig S., Fauci A. S., Benn S., Rabson A., Daugherty D., Gendelman H. E., Hoggan M. D., Venkotesan S., Martin M. A. 1986; Biological and biochemical characterisation of a cloned Leu3 cell line surviving infection with the acquired immunodeficiency syndrome retrovirus. Journal of Experimental Medicine 164:280–290
    [Google Scholar]
  8. Fung M. S. C., Sun C. R. Y., Gordon W. L., Liou R.-S., Chang T. W., Sun W. N. C., Daar E. S., Ho D. D. 1992; Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120. Journal of Virology 66:848–856
    [Google Scholar]
  9. Gelderblom H. R., Hausmann E. H., Ozel M., Pauli G., Koch M. A. 1987; Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology 156:171–176
    [Google Scholar]
  10. Hansen M. B., Nielsen S. E., Berg K. 1989; Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods 119:203–210
    [Google Scholar]
  11. Harvey M. A., Aldorini L., Miller A., Sercarz E. E. 1979; Lysozyme-induced T-suppressor cells and antibodies have a predominant idiotype. Nature; London: 281594–596
    [Google Scholar]
  12. Kessler S. W. 1975; Rapid isolation of antigens from cells with a staphylococcal Protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. Journal of Immunology 115:1617–1624
    [Google Scholar]
  13. Kowalski M., Potz J., Basiripor L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. 1987; Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science 237:1351–1355
    [Google Scholar]
  14. Krowka J. F., Singh B., Stites D. P., Maino V. C., Narindray D., Hollander H., Jain S., Chen H., Blackwood L., Steimer K. S. 1991; Epitopes of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins recognized by antibodies in the sera of HIV-1-infected individuals. Clinical Immunology and Immunopathology 59:53–64
    [Google Scholar]
  15. Kuroda K., Geyer H., Geyer R., Doerfler W., Klenk H.-D. 1990; The oligosaccharides of influenza hemagglutinin expressed in insect cells by a baculovirus vector. Virology 174:418–429
    [Google Scholar]
  16. Kuroda K., Veit M., Klenk H.-D. 1991; Retarded processing of influenza hemagglutinin in insect cells. Virology 180:159–165
    [Google Scholar]
  17. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature; London: 227680–685
    [Google Scholar]
  18. Mckeating J. A., Shotton C., Cordell J., Graham S., Balfe P., Sullivan N., Charles M., Page M., Bolmstedt A., Olofsson S., Kayman S. C., Wu Z., Pinter A., Dean C., Sodroski J., Weiss R. A. 1993; Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120. Journal of Virology 67:4932–4944
    [Google Scholar]
  19. Maddon P. J., Dalgleish A. G., Mcdougal J. S., Clapham P. R., Weiss R. A., Axel R. 1986; The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333–348
    [Google Scholar]
  20. Metzger D. W., Ch’ng L. K., Miller A., Sercarz E. E. 1984; The expressed lysozyme specific B-cell repertoire. I. heterogeneity in the monoclonal anti-hen egg white lysozyme specificity repertoire and its difference from the in situ repertoire. European Journal of Immunology 14:87–93
    [Google Scholar]
  21. Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. 1987; Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. Journal of Virology 61:570–578
    [Google Scholar]
  22. Moore J. P., Sattentau Q. J., Yoshiyama H., Thali M., Charles M., Sullivan N., Poon S.-W., Fung M. S., Traincard F., Pinkus M., Robey G., Robinson J. E., Ho D. D., Sodroski J. 1993; Probing the structure of the V2 domain of human immunodeficiency virus type 1 surface glycoprotein gpl20 with a panel of eight monoclonal antibodies: human immune responses to the VI and V2 domains. Journal of Virology 67:6136–6151
    [Google Scholar]
  23. Morrison L. A., Lukacher A., Braciale V. L., Fan D. P., Braciale T. J. 1986; Differences in antigen presentation to MHC class I and class II restricted influenza virus-specific cytolytic T-lymphocyte clones. Journal of Experimental Medicine 163:903–921
    [Google Scholar]
  24. Mossman T. 1983; Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65:55–63
    [Google Scholar]
  25. Neurath A. R., Strick N., Lee E. S. Y. 1990; B cell epitope mapping of human immunodeficiency virus envelope glycoproteins with long (19- to 36-residue) synthetic peptides. Journal of General Virology 71:85–95
    [Google Scholar]
  26. Niedrig M., Harthus H.-P., Hinkula J., Bröker M., Bickhard H., Pauli G., Gelderblom H. R., Wahren B. 1992; Inhibition of viral replication by monoclonal antibodies directed against human immunodeficiency virus gp120. Journal of General Virology 73:2451–2455
    [Google Scholar]
  27. Palker T. J., Matthews T. J., Clark M. E., Cianciolo G. J., Randall R. R., Langlois A. J., White G. C., Safai B., Snyderman R., Bolognesi D. P., Haynes B. F. 1987; A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope. Proceedings of the National Academy of Sciences, U.S.A 84:2479–2483
    [Google Scholar]
  28. Pauwels R., Balzarini J., Baba M., Snoeck R., Schols D., Herdewija P., Desmyter J., Clercq E. 1988; Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. Journal of Virological Methods 20:309–321
    [Google Scholar]
  29. Pitts T. W., Bohanon M. J., Leach M. F., Mcquade T. J., Marschke C. K., Merritt J. A., Wierenga W., Nicholas J. A. 1991; Soluble CD4-PE40 is cytotoxic for a transfected mammalian cell line stably expressing the envelope protein of human immunodeficiency virus (HIV-1), and cytotoxicity is variably inhibited by the sera of HIV-1-infected patients. AIDS Research and Human Retroviruses 7:741–750
    [Google Scholar]
  30. Redfield R. R., Birx D. L., Ketter N., Tramont E., Polonis V., Davis C., Brundage J. F., Smith G., Johnson S., Fowler A., Wierzba T., Shafferman A., Volvovitz F., Oster C., Burke D. S. 1991; A phase 1 evaluation of the safety and immunogenicity of vaccination with recombinant gpl60 in patients with early human immunodeficiency virus infection. New England Journal of Medicine 324:1677–1684
    [Google Scholar]
  31. Rubino K. L., Nicholas J. A. 1992; A novel, spectrophotometric microneutralization assay for respiratory syncytial virus. Journal of Virological Methods 39:55–67
    [Google Scholar]
  32. Salahuddin S. Z., Markham P. D., Wong-Staal F., Franchini G., Kalyanaraman V. S., Gallo R. C. 1983; Restricted expression of human T-cell leukemia-lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes. Virology 129:51–64
    [Google Scholar]
  33. Schlesinger J. J., Brandriss M. W., Monath T. P. 1983; Monoclonal antibodies distinguish between wild and vaccine strains of yellow fever virus by neutralization, hemagglutination inhibition and immune precipitation of the virus envelope protein. Virology 125:8–17
    [Google Scholar]
  34. Schwartz D. H., Gorse G., Clements M. L., Belshe R., Izu A., Duliege A.-M., Berman P., Twaddell T., Stablein D., Sposto R., Siliciano R., Matthews T. J. 1993; Induction of HIV-1 neutralising and syncytium inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine. Lancet 342:69–73
    [Google Scholar]
  35. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. 1984; Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immunodeficiency syndrome. Science 226:1165–1171
    [Google Scholar]
  36. Shulman M., Wilde C., Köhler G. 1978; A better cell line for making hybridomas secreting specific antibodies. Nature; London: 276269–270
    [Google Scholar]
  37. Smith G. E., Ju G., Ericson B. L., Moshera J., Lahm H.-W., Chizzonite R., Summer M. D. 1985; Modification and secretion of human interleukin 2 produced in insect cells by a baculovirus expression vector. Proceedings of the National Academy of Sciences, U.S.A 82:8404–8408
    [Google Scholar]
  38. Stephens D. M., Eichberg J. W., Haigwood N. L., Steimer K. S., Davis D., Lachmann P. J. 1992; Antibodies are produced to the variable regions of the external envelope glycoprotein of human immunodeficiency virus type 1 in chimpanzees infected with the virus and baboons immunized with a candidate recombinant vaccine. Journal of General Virology 73:1099–1106
    [Google Scholar]
  39. Thiriart C., Francotte M., Cohen J., Collignon C., Delers A., Kummert S., Molitor C., Gilles D., Roelants P., Van Wijnendaele F., De Wilde M., Bruck C. 1989; Several antigenic determinants exposed on the gp120 moeity of HIV-1 gp160 are hidden on the mature gp120. Journal of Immunology 143:1832–1836
    [Google Scholar]
  40. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, U.S.A 76:4350–4354
    [Google Scholar]
  41. Vahlne A., Horal P., Eriksson K., Jeansson S., Rymo L., Hedstrom K. G., Czerkinsky C., Holmgren J., Svennerholm B. 1991; Immunizations of monkeys with synthetic peptides disclose conserved areas on gp120 of human immunodeficiency virus type 1 associated with cross-neutralizing antibodies and T-cell recognition. Proceedings of the National Academy of Sciences, U.S.A 88:10744–10748
    [Google Scholar]
  42. Viscidi R., Ellerbeck E., Garrison L., Midthun K., Clements M. L., Clayman B., Fernie B., Smith G. 1990; Characterization of serum antibody responses to recombinant HIV-1 gp160 vaccine by enzyme immunoassay. AIDS Research and Human Retroviruses 6:1251–1256
    [Google Scholar]
  43. Wicker L. S., Benjamin C. D., Katz M. E., Sercarz E. E., Miller A. 1982; The similar and highly restrictive epitope specificity of Ts and primary B cells. Federation Proceedings 41:302
    [Google Scholar]
  44. Wyatt R., Sullivan N., Thali M., Repke H., Ho D., Robinson J., Posner M., Sodroski J. 1993; Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. Journal of Virology 67:4557–4565
    [Google Scholar]
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