Raphael GottardoRobert T. BailerBette T. KorberS. GnanakaranJoshua PhillipsXiaoying ShenGeorgia D. TomarasEllen TurkGregory ImholteLarry EcklerHolger WenschuhJohannes ZerweckKelli GreeneHongmei GaoPhillip W. BermanDonald FrancisFaruk SinangilCarter LeeSorachai NitayaphanSupachai Rerks-NgarmJaranit KaewkungwalPunnee PitisuttithumJames TartagliaMerlin L. RobbNelson L. MichaelJerome H. KimSusan Zolla-PaznerBarton F. HaynesJohn R. MascolaSteve SelfPeter GilbertDavid C. MontefioriFred Hutchinson Cancer Research CenterNational Institute of Allergy and Infectious DiseasesLos Alamos National LaboratoryDuke University School of MedicineJPT Peptide Technologies GmbHUniversity of California, Santa CruzGlobal Solutions for Infectious DiseasesArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthMahidol UniversityDepartment of Research and DevelopmentWalter Reed Army Institute of ResearchVA Medical CenterNYU School of Medicine2018-10-192018-10-192013-09-26PLoS ONE. Vol.8, No.9 (2013)193262032-s2.0-84884608718https://repository.li.mahidol.ac.th/handle/123456789/30979Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1371/journal.pone.0075665