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Defining antibody protection against HIV-1 transmission in Hu-PBL-SCID mice
1Aaron Diamond AIDS Research Center, New York, NY 10016, USA.
Multiple monoclonal and polyclonal antibody preparations have been shown to neutralize HIV-1 infection in vitro. Upon direct testing in humans, however, many of these have failed to demonstrate clinical efficacy. Hu-PBL-SCID mice offer a model system in which to test the pre-clinical efficacy of antibody preparations. Testing in hu-PBL-SCID mice has shown that some antibodies are able to mediate pre- and post-exposure protection against HIV-1 infection, at concentrations that should be attainable in humans. Despite differences in the route and mode of transmission in humans and in hu-PBL-SCID mice, several aspects of the model make it a favorable model for future testing of antibody protection against HIV-1 infection. These include the architecture of the peritoneal cavity, the mixture of human cells that engraft, the density of human target cells for HIV-1 infection, and the presence of complement and NK cells that can interact with antibody preparations in blocking HIV-1 infection. The use of this model in testing newer antibody preparations for efficacy against primary isolates should enhance our knowledge of the mechanisms of antibody protection against HIV-1 infection in vivo and speed the pre-clinical evaluation of potential immunoprophylactic agents against HIV-1.
Multiple monoclonal and polyclonal antibody preparations have been shown to neutralize HIV-1 infection in vitro. Upon direct testing in humans, however, many of these have failed to demonstrate clinical efficacy. Hu-PBL-SCID mice offer a model system in which to test the pre-clinical efficacy of antibody preparations. Testing in hu-PBL-SCID mice has shown that some antibodies are able to mediate pre- and post-exposure protection against HIV-1 infection, at concentrations that should be attainable in humans. Despite differences in the route and mode of transmission in humans and in hu-PBL-SCID mice, several aspects of the model make it a favorable model for future testing of antibody protection against HIV-1 infection. These include the architecture of the peritoneal cavity, the mixture of human cells that engraft, the density of human target cells for HIV-1 infection, and the presence of complement and NK cells that can interact with antibody preparations in blocking HIV-1 infection. The use of this model in testing newer antibody preparations for efficacy against primary isolates should enhance our knowledge of the mechanisms of antibody protection against HIV-1 infection in vivo and speed the pre-clinical evaluation of potential immunoprophylactic agents against HIV-1.