Anti-CD4 Anti-Idiotype Antibodies in Volunteers Immunized with rgp 160 of HIV-1 or Infected with HIV-1

Abstract

We examined the sera of volunteers vaccinated with recombinant gp160 of human immunodeficiency virus type 1 (HIV-1) and control volunteers for the presence of anti-(anti-gp160 idiotype) antibodies which antigenically mimic gp160 and, therefore, bind to CD4 on human cells. Anti-CD4 antibodies were detected in the sera of 3 of 5 rgp160 recipients and 1 of 5 controls by indirect immunofluorescence using CD4-transfected HeLa cells or enzyme-linked immunosorbent assay (ELISA) using recombinant soluble CD4 as the solid phase. The control volunteer who was positive subsequently developed antibodies to HIV-1 by Western blot analysis. The anti-CD4 antibodies detected in the sera of the rgp160 vaccinees and the control volunteer appeared to be anti-idiotypic in nature, reacting with a paratope expressed on goat anti-gp160 antibodies but not on antibodies from normal goat serum. Binding to either transfected CD4+ HeLa cells or blotted anti-gp160 serum could be inhibited by preincubating the anti-CD4 serum with soluble CD4, or preincubating the cells or blotted anti-gp160 serum with recombinant gp160. Anti-CD4 antibodies were initially detectable only after the antibody response to gp160 began to decrease in the vaccinees, and the HIV-1-infected volunteer mounted a detectable anti-HIV-1 antibody response only after a decline in the anti-CD4 antibodies in his serum. These data strongly suggest that anti-CD4 antibodies which are anti-idiotypic to a paratope expressed on anti-gp160 antibodies are generated in response to both vaccination with rgp160 and infection with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

“…In natural HIV infection, where gp120-CD4 complexes frequently form, putative anti-CD4 autoantibodies have been detected in roughly 10% of subjects studied (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). These antibodies seem directed against the D3 and D4 regions of CD4 (59,61,66,67), are not immunoreactive with cell surface CD4 (56,58,59,66), and lack detectable biological activity in vitro (58,66).…”

“…It is estimated that 10% of HIV-positive (HIV ϩ ) individuals develop anti-CD4 autoantibodies for unknown reasons. Any role for these responses in HIV infection or pathogenesis remains equivocal (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). Thus, comprehensive analyses in relevant experimental models are needed to answer this question.…”

Antigenic complementarity among AIDS-associated infectious agents and molecular mimicry of lymphocyte proteins as inducers of lymphocytotoxic antibodies and circulating immune complexes

“…One is the intrinsic risk of inducing lymphocytotoxic antibodies using whole organism vaccines against any of the agents described here as having antigens that may elicit antibodies that mimic lymphocyte antigens. The risk is real, since HIV vaccine preparations employing recombinant gp160 have already been demonstrated to induce anti-CD4 anti-idiotype antibodies (Keay et al, 1992). The second issue involves testing the safety of any vaccine that is to be delivered to individuals characterized by pre-existing, multiple, concurrent infections.…”

Anti-CD4 Antibodies are Associated with HIV-1 Seroconversion and May Be Detectable Before Anti-HIV-1 Antibodies

“…These anti-CD4 antibodies were able to bind specifically to affinity-purified goat anti-rgpl60 antibodies, and this binding could be inhibited by preincubating the blotted goat antibodies with rgp 160 or by preincubating the patients' sera with rsCD4. 16 We now have found anti-CD4 antibodies in 12 of 14 (86%) of HIV-1 seroconverters that we tested. Of the 13 individuals for whom a "seroconverting" serum sample was available, 11 had antibodies to CD4.…”