Designing Immunity to Hiv: Manipulating Antibody-Dependent Cellular Cytotoxicity Antibodies

Abstract

The failure of HIV vaccine concepts based upon either simple antibody or T-cell immunity means that newer concepts in immunity to HIV require urgent investigation. Antibody-dependent cellular cytotoxicity (ADCC) responses, utilizing the arms of humoral and innate immunity, have been studied for many years, but their role in controlling or preventing HIV-1 remains controversial. Newer technologies can now be applied to study and map ADCC responses. This permits experiments to purify and isolate HIV-specific ADCC antibodies and directly assess their role in preventing simian–HIV infections in macaques. Analogous to complexities in the quality and specificity of T-cell and neutralizing antibody immunity to HIV, it is likely that some ADCC antibodies will be more efficient than others in controlling HIV infection and limiting viral escape. Rationally defining broadly reactive ADCC antibodies with potent in vivo activity should allow the selection of the most appropriate ADCC-inducing vaccine antigens. This pathway towards manipulating ADCC antibodies, which control HIV infection, will ultimately improve our understanding of ADCC against HIV infection and potentially yield new HIV vaccine candidates.