Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial

被引：202

作者：

Gottardo, Raphael ^{[1
]}

Bailer, Robert T. ^{[2
]}

Korber, Bette T. ^{[3
]}

Gnanakaran, S. ^{[3
]}

Phillips, Joshua ^{[3
]}

Shen, Xiaoying ^{[4
]}

Tomaras, Georgia D. ^{[4
]}

Turk, Ellen ^{[2
]}

Imholte, Gregory ^{[1
]}

Eckler, Larry ^{[5
]}

Wenschuh, Holger ^{[5
]}

Zerweck, Johannes ^{[5
]}

Greene, Kelli ^{[4
]}

Gao, Hongmei ^{[4
]}

Berman, Phillip W. ^{[6
]}

Francis, Donald ^{[7
]}

Sinangil, Faruk ^{[7
]}

Lee, Carter ^{[7
]}

Nitayaphan, Sorachai ^{[8
]}

Rerks-Ngarm, Supachai ^{[9
]}

Kaewkungwal, Jaranit ^{[10
]}

Pitisuttithum, Punnee ^{[11
,12
]}

Tartaglia, James ^{[13
]}

Robb, Merlin L. ^{[14
]}

Michael, Nelson L. ^{[14
]}

Kim, Jerome H. ^{[14
]}

Zolla-Pazner, Susan ^{[15
,16
]}

Haynes, Barton F. ^{[4
]}

Mascola, John R. ^{[2
]}

Self, Steve ^{[1
]}

Gilbert, Peter ^{[1
]}

Montefiori, David C. ^{[4
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[2] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[3] Los Alamos Natl Lab, Los Alamos, NM USA

[4] Duke Univ, Med Ctr, Durham, NC 27710 USA

[5] JPT Peptide Technol GmbH, Berlin, Germany

[6] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA

[7] Global Solut Infect Dis, San Francisco, CA USA

[8] US Army Med Component, Dept Retrovirol, AFRIMS, Bangkok, Thailand

[9] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand

[10] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPHI, Bangkok, Thailand

[11] Mahidol Univ, Vaccine Trial Ctr, Bangkok 10700, Thailand

[12] Mahidol Univ, Dept Clin Trop Med, Bangkok 10700, Thailand

[13] Sanofi Pasteur, Dept Res & Dev, Swiftwater, PA USA

[14] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA

[15] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA

[16] NYU, Sch Med, New York, NY USA

来源：

PLOS ONE | 2013年 / 8卷 / 09期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; DEPENDENT CELLULAR CYTOTOXICITY; RECOMBINANT GLYCOPROTEIN-120 VACCINE; CD4; BINDING-SITE; ENVELOPE PROTEIN; NEUTRALIZING ANTIBODIES; CONFORMATIONAL EPITOPE; TRANSMEMBRANE PROTEIN; BROAD NEUTRALIZATION;

D O I：

10.1371/journal.pone.0075665

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neutralizing 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.

引用

页数：16

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