Hua Xin LiaoMattia BonsignoriS. Munir AlamJason S. McLellanGeorgia D. TomarasM. Anthony MoodyDaniel M. KozinkKwan Ki HwangXi ChenChun Yen TsaoPinghuang LiuXiaozhi LuRobert J. ParksDavid C. MontefioriGuido FerrariJustin PollaraMangala RaoKristina K. PeachmanSampa SantraNorman L. LetvinNicos KarasavvasZhi Yong YangKaifan DaiMarie PanceraJason GormanKevin WieheNathan I. NicelySupachai Rerks-NgarmSorachai NitayaphanJaranit KaewkungwalPunnee PitisuttithumJames TartagliaFaruk SinangilJerome H. KimNelson L. MichaelThomas B. KeplerPeter D. KwongJohn R. MascolaGary J. NabelAbraham PinterSusan Zolla-PaznerBarton F. HaynesDuke University School of MedicineNational Institutes of Health, BethesdaWalter Reed Army Institute of ResearchHarvard Medical SchoolArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthMahidol UniversitySanofi PasteurGlobal Solutions for Infectious DiseasesBoston University School of MedicineRutgers New Jersey Medical SchoolVA Medical CenterNYU School of Medicine2018-10-192018-10-192013-01-24Immunity. Vol.38, No.1 (2013), 176-18610974180107476132-s2.0-84872809067https://repository.li.mahidol.ac.th/handle/20.500.14594/31974The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4+T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the β strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options. © 2013 Elsevier Inc.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1016/j.immuni.2012.11.011