Georgia D. TomarasGuido FerrariXiaoying ShenS. Munir AlamHua Xin LiaoJustin PollaraMattia BonsignoriM. Anthony MoodyYouyi FongXi ChenBrigid PolingCindo O. NicholsonRuijun ZhangXiaozhi LuRobert ParksJaranit KaewkungwalSorachai NitayaphanPunnee PitisuttithumSupachai Rerks-NgarmPeter B. GilbertJerome H. KimNelson L. MichaelDavid C. MontefioriBarton F. HaynesDuke University School of MedicineStatistical Center for HIV/AIDS Research and PreventionMahidol UniversityArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthUS Military HIV Research Program2018-10-192018-10-192013-05-28Proceedings of the National Academy of Sciences of the United States of America. Vol.110, No.22 (2013), 9019-902410916490002784242-s2.0-84878430727https://repository.li.mahidol.ac.th/handle/123456789/32828Analysis of correlates of risk of infection in the RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (Env) variable region 1 and 2 inversely correlatedwith risk, whereas HIV-1 Env-specific plasma IgA responses directly correlated with risk. In the secondary analysis, antibody-dependent cellular cytotoxicity (ADCC) was another inverse correlate of risk, but only in the presence of low plasma IgA Env-specific antibodies. Thus, we investigated the hypothesis that IgA could attenuate the protective effect of IgGresponses throughcompetitionfor thesameEnvbinding sites. We report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. Moreover, Env-specific IgA antibodies from RV144 vaccinees blocked the binding of ADCC-mediating mAb to HIV-1 Env glycoprotein 120 (gp120). An Env-specific monomeric IgA mAb isolated from an RV144 vaccinee also inhibited the ability of natural killer cells to kill HIV-1-infected CD4+T cells coated with RV144-induced IgG antibodies. We show that monomeric Env-specific IgA, as part of postvaccination polyclonal antibody response, may modulate vaccine-induced immunity by diminishing ADCC effector function.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.1073/pnas.1301456110