Mattia BonsignoriJustin PollaraAnthony A. MoodyXi ChenKwan Ki HwangThaddeus C. GurleyDaniel M. KozinkDawn J. MarshallJohn F. WhitesidesChun Yen TsaoGeorgia D. TomarasDavid C. MontefioriGuido FerrariHua Xin LiaoBarton F. HaynesMichael D. AlpertDavid T. EvansPeter B. GilbertYing HuangJaranit KaewkungwalSorachai NitayaphanPunnee PitisuttithumSupachai Rerks-NgarmJerome H. KimNelson L. MichaelGeorge K. LewisAnthony DeVicoDuke University School of MedicineHarvard Medical SchoolFred Hutchinson Cancer Research CenterMahidol UniversityArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthU.S. Military HIV Research ProgramUniversity of Maryland School of Medicine2018-06-112018-06-112012-11-01Journal of Virology. Vol.86, No.21 (2012), 11521-11532109855140022538X2-s2.0-84867902474https://repository.li.mahidol.ac.th/handle/20.500.14594/14248The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesisis that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment.Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n=19), a non-A32-blockable conformational epitope (n=1), and the gp120 Env variable loops (n=3). Fourteen antibodies mediated cross-clade target cell killing.ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs. © 2012, American Society for Microbiology.Mahidol UniversityImmunology and MicrobiologyArticleSCOPUS10.1128/JVI.01023-12