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Infection enhancement and complement activation by human gp41 antibodies.




 

Int Conf AIDS. 1994 Aug 7-12;10(2):85 (abstract no. PA0219). Unique

OBJECTIVE: Little is known about the mechanism of complement-dependent enhancement of HIV infection (CDEI). Antibodies responsible for CDEI may play a significant role in the progression of HIV disease according to our recent studies (Fust et al., AIDS, in press). In the present work, a possible correlation between CDEI and complement activation was studied by using 3 human anti-gp41 monoclonals (a kind gift of Dr. S. Zolla-Pazner, New York) and a polyclonal human anti-gp41 preparation. METHODS: Complement activation by the antibodies was tested in gp41-coated ELISA plates. Binding of C1q, C3b, C4b and IgG to the plates incubated with mixtures of different amounts of antibodies and normal human serum (NHS) was measured. CDEI was determined as described previously (D. Toth et al., AIDS, 1991) using mixtures of different dilutions of the antibody preparations and 1:4 or 1:40 final NHS dilution; HTLVIIIb, and CR2 carrying MT-4 target cells. Growth of HIV in the cultures was monitored by RT assay. RESULTS: All 3 monoclonals (181-D, 240-D, 246-D) increased the C1q binding ability of solid phase gp41, the effect of 246-D was the highest. C3b and C4b binding from NHS was increased only by the mAb 246-D and the polyclonal antibody. A significant decrease in antibody binding to gp41 was observed with each antibody preparation in the presence of both NHS and purified C1q, similarly to our earlier results (Hidvegi et al. 1993). All 3 monoclonals had a marked CDEI effect. The peak RT activity in the cultures was significantly higher at the higher NHS concentration. The extent of CDEI was dependent on the antibody concentration as well. DISCUSSION AND CONCLUSIONS: Similarly to our previous results obtained with sera of HIV patients, human anti-gp41 monoclonals had a marked CDEI effect, especially at near-physiological concentrations of complement. The extent of CDEI, however, did not correlate with the ability of the antibodies to increase complement activation by gp41. Further studies are necessary to explain the mechanism of complement-dependent HIV infection enhancement.

Antibodies, Monoclonal/IMMUNOLOGY/METABOLISM Complement Activation/*IMMUNOLOGY Complement 1q/IMMUNOLOGY/METABOLISM Complement 3b/IMMUNOLOGY/METABOLISM Complement 4b/IMMUNOLOGY/METABOLISM Enzyme-Linked Immunosorbent Assay Human HIV Antibodies/*IMMUNOLOGY/METABOLISM HIV Envelope Protein gp41/*IMMUNOLOGY HIV Infections/*IMMUNOLOGY IgG/IMMUNOLOGY/METABOLISM ABSTRACT



 




Information in this article was accurate in December 30, 1994. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.