CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination.
Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120 immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule. The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg IOT4a. Six booster injections followed until day 35. Sera from study patients, 80 HIV-positive, and 43 seronegative controls were examined by a panel of assays, including an ELISA using competition against biotinylated recombinant CD4, flow cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase in competitive binding activity, which was quantitative in ELISA and flow cytometry, was observed. In the ELISA, competition against biotin-CD4 was quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in the assays employed, while 5/80 HIV sera showed binding qualities similar to vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120 binding to CD4.
Division of Clinical Immunology, Hannover Medical School, Germany.
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PM
Deckert
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Ballmaier
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S
Lang
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Deicher
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Schedel
D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology*; D003429:Cross Reactions; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D008297:Male; D051379:Mice; D008875:Middle Aged; D018716:Molecular Mimicry; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins