David EasterhoffJustin PollaraKan LuoBenjamin JanusNeelakshi GohainLa Tonya D. WilliamsMatthew Zirui TayAnthony MonroeKristina PeachmanMisook ChoeSusie MinPaolo LussoPeng ZhangEden P. GoHeather DesaireMattia BonsignoriKwan Ki HwangCharles BeckMatina KakalisRobert J. O’ConnellSandhya VasanJerome H. KimNelson L. MichaelJean Louis ExclerMerlin L. RobbSupachai Rerks-NgarmJaranit KaewkungwalPunnee PitisuttithumSorachai NitayaphanFaruk SinangilJames TartagliaSanjay PhogatKevin WieheKevin O. SaundersDavid C. MontefioriGeorgia D. TomarasM. Anthony MoodyJames ArthosMangala RaoM. Gordon JoyceGilad OfekGuido FerrariBarton F. HaynesDuke University Medical CenterGlaxoSmithKline SpAInternational Vaccine Institute, SeoulSanofi Pasteur SANational Institute of Allergy and Infectious DiseasesArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthUniversity of Kansas, LawrenceHJFWalter Reed Army Institute of ResearchMahidol UniversityDuke University School of MedicineUniversity of MarylandHealth PolicyGlobal Solutions for Infectious Diseases2020-03-262020-03-262020-01-30JCI Insight. Vol.5, No.2 (2020)237937082-s2.0-85079185722https://repository.li.mahidol.ac.th/handle/20.500.14594/53780© 2020, American Society for Clinical Investigation. In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2–specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope–specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti–HIV-1 effector functions.Mahidol UniversityMedicineArticleSCOPUS10.1172/jci.insight.131437