CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination

• Published in: The Journal of immunology (1950) Vol. 156; no. 2; pp. 826 - 833
• Main Authors: Deckert, PM, Ballmaier, M, Lang, S, Deicher, H, Schedel, I
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.1996
• Subjects: Adult; AIDS/HIV; Animals; Antibodies, Anti-Idiotypic - blood; Antibodies, Anti-Idiotypic - immunology; Antibodies, Anti-Idiotypic - therapeutic use; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibody Specificity; CD4 Antigens - immunology; Cross Reactions; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; HIV Envelope Protein gp120 - immunology; HIV Infections - blood; HIV Infections - immunology; HIV Infections - therapy; HIV-1 - immunology; human immunodeficiency virus; Humans; Immunotherapy, Active; Male; Mice; Middle Aged; Molecular Mimicry; Rabbits; Recombinant Proteins - immunology; Vaccination
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.156.2.826

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.