HIV-Specific ADCC Antibodies in HIV Prevention
HIV-Specific ADCC Antibodies in HIV Prevention
Both CTL and NAb against HIV lead to rapid selection for immune escape variants during HIV infection, which is one reason that HIV is difficult to control. If ADCC antibodies exert pressure on HIV replication, we would expect to see mutational escape selected by ADCC antibodies also. Indeed, Chung et al. mapped a series of linear ADCC epitopes, some of which were non-neutralizing epitopes, and showed evolution of sequences across several ADCC epitopes towards variants with reduced ADCC recognition. This study shows proof-of-principle of the in-vivo pressure applied by ADCC antibodies during HIV infection. It is also interesting to note that the HIV strains obtained from vaccinated individuals in the RV144 trial were enriched for variants of Env sequences that may also reflect immune escape variants. Acharya et al. recently performed a detailed structural analysis of the cluster of ADCC epitopes targeting the C1 region of Env implicated as a possible target of protective responses induced by the RV144 trial. Both antibody orientation and the ability to form multivalent antigen–antibody complexes were important determinants of ADCC potency.
Mutational Escape to Avoid HIV-Specific Antibody-Dependent Cellular Cytotoxicity Immunity
Both CTL and NAb against HIV lead to rapid selection for immune escape variants during HIV infection, which is one reason that HIV is difficult to control. If ADCC antibodies exert pressure on HIV replication, we would expect to see mutational escape selected by ADCC antibodies also. Indeed, Chung et al. mapped a series of linear ADCC epitopes, some of which were non-neutralizing epitopes, and showed evolution of sequences across several ADCC epitopes towards variants with reduced ADCC recognition. This study shows proof-of-principle of the in-vivo pressure applied by ADCC antibodies during HIV infection. It is also interesting to note that the HIV strains obtained from vaccinated individuals in the RV144 trial were enriched for variants of Env sequences that may also reflect immune escape variants. Acharya et al. recently performed a detailed structural analysis of the cluster of ADCC epitopes targeting the C1 region of Env implicated as a possible target of protective responses induced by the RV144 trial. Both antibody orientation and the ability to form multivalent antigen–antibody complexes were important determinants of ADCC potency.
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