Convergentsynergistic Passive Immunotherapy

Enhanced or synergistic neutralizing effects in vitro have been reported utilizing human monoclonal antibodies in combinations, e.g., anti-V3 and CD4bd antibodies.33-35

Using a chimeric simian immunodeficiency virus (SHIV-vpw+) which expressed HIV-1 IIIB envelope antigens, the lowest effective antibody concentration for 90% viral neutralization was achieved with combinations of monoclonal antibodies b12, 2F5, 2G12, and anti-V3 694/98D, and, depending on the combination regimen, the concentration of monoclonal antibodies required to reach 90% virus neutralization was reduced approximately 2- to 25-fold as compared to the dose requirement of individual monoclonal antibodies to produce an equivalent effect.36 Therefore, com binations of monoclonal antibodies may have a role in passive immuno-prophylaxis against HIV-1, as indicated by the synergy noted in the combination regimens.

However, it must be noted that in another case of combined regimens a cocktail of 10 monoclonal antibodies could not neutralize one primary isolate, designated US4.37 Additionally, this non-syncytium-inducing strain was neutralization-resistant when tested individually using a panel of 17 monoclonal antibodies which also included b12 and 2F5.

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