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Stimulation of HIV-1-neutralizing antibodies in simian HIV-IIIB-infected macaques

The humoral immune response to HIV type 1 (HIV-1) infection is inadequate in part because of the narrow range of virus-neutralizing antibodies elicited by the initially infecting virus and the failure to recognize subsequently arising virus variants.

Determination of Neutralizing Activity of Antibodies Against HIV-1 IIIB and MN.
A quantitative syncytium-forming microassay was employed for detection of the virus-neutralizing antibody response (13). Neutralization titers were determined by using two HIV-1 strains, HIV-1 IIIB and HIV-1 MN. A virus-syncytial-sensitive clone of CEM cells (CEM-SS) develops quantifiable, adherent syncytia (syncytium-forming units; SFUs) on a background of confluent, normal CEM monolayer in 4–6 days.

Statistical Analysis of Antibody Responses.
Viral antigen-binding antibodies and HIV-1 IIIB- and MN-neutralizing antibody titers were subjected to statistical analysis to determine the significance of changes observed after vaccination with mAb 1F7 or control mAb TEPC 183.

Analysis of Virus Neutralization Potency.
Blood samples from the three monkeys injected with mAb 1F7 and the control monkey injected with TEPC 183 were analyzed before, during, and after the vaccination regimen. Serial dilution of plasma specimens collected at different time points during the observation period were analyzed for virus-neutralizing antibody activity by using a quantitative syncytia-forming microassay (13) and HIV-1 strains IIIB and MN. The neutralization activity for HIV-1 IIIB and for HIV-1 MN was derived from five plasma dilutions at day 0 (prebleed), and four times after day 0 for each macaque.

Antibody neutralization activity for HIV-1 IIIB increased significantly after four inoculations of 1F7 in monkey 149-93 as determined at day 31