HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities

Justin PollaraMattia BonsignoriM. Anthony MoodyPinghuang LiuS. Munir AlamKwan Ki HwangThaddeus C. GurleyDaniel M. KozinkLawrence C. ArmandDawn J. MarshallJohn F. WhitesidesJaranit KaewkungwalSorachai NitayaphanPunnee PitisuttithumSupachai Rerks-NgarmMerlin L. RobbRobert J. O'ConnellJerome H. KimNelson L. MichaelDavid C. MontefioriGeorgia D. TomarasHua Xin LiaoBarton F. HaynesGuido FerrariDuke University Medical CenterMahidol UniversityArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthUS Military HIV Research Program2018-11-092018-11-092014-01-01Journal of Virology. Vol.88, No.14 (2014), 7715-7726109855140022538X2-s2.0-84904113226https://repository.li.mahidol.ac.th/handle/20.500.14594/33160The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which is included in the epitope recognized by vaccinee-derived V2 monoclonal antibodies. The ALVAC/AIDSVax vaccine induced antibody-dependent cellular cytotoxicity (ADCC) against the Env V2 and constant 1 (C1) regions. In the presence of low IgA Env antibody levels, plasma levels of ADCC activity correlated with lower risk of infection. In this study, we demonstrate that C1 and V2 monoclonal antibodies isolated from RV144 vaccinees synergized for neutralization, infectious virus capture, and ADCC. Importantly, synergy increased the HIV-1 ADCC activity of V2 monoclonal antibody CH58 at concentrations similar to that observed in plasma of RV144 vaccinees. These findings raise the hypothesis that synergy among vaccine-induced antibodies with different epitope specificities contributes to HIV-1 antiviral antibody responses and is important to induce for reduction in the risk of HIV-1 transmission. © 2014, American Society for Microbiology.Mahidol UniversityAgricultural and Biological SciencesImmunology and MicrobiologyHIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activitiesArticleSCOPUS10.1128/JVI.00156-14