Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial

被引：1490

作者：

Haynes, Barton F. ^{[1
,2
]}

Gilbert, Peter B. ^{[3
]}

McElrath, M. Juliana ^{[4
]}

Zolla-Pazner, Susan ^{[5
,6
]}

Tomaras, Georgia D. ^{[1
,2
]}

Alam, S. Munir ^{[1
,2
]}

Evans, David T. ^{[7
]}

Montefiori, David C. ^{[1
,2
]}

Karnasuta, Chitraporn ^{[10
]}

Sutthent, Ruengpueng ^{[12
]}

Liao, Hua-Xin ^{[1
,2
]}

DeVico, Anthony L. ^{[16
]}

Lewis, George K. ^{[16
]}

Williams, Constance ^{[5
,6
]}

Pinter, Abraham ^{[17
]}

Fong, Youyi ^{[3
]}

Janes, Holly ^{[3
]}

DeCamp, Allan ^{[3
]}

Huang, Yunda ^{[3
]}

Rao, Mangala ^{[8
]}

Billings, Erik ^{[8
]}

Karasavvas, Nicos ^{[10
]}

Robb, Merlin L. ^{[8
]}

Ngauy, Viseth ^{[10
]}

de Souza, Mark S. ^{[10
]}

Paris, Robert ^{[8
]}

Ferrari, Guido ^{[1
,2
]}

Bailer, Robert T. ^{[9
]}

Soderberg, Kelly A. ^{[1
,2
]}

Andrews, Charla ^{[8
]}

Berman, Phillip W. ^{[15
]}

Frahm, Nicole ^{[4
]}

De Rosa, Stephen C. ^{[4
]}

Alpert, Michael D. ^{[7
]}

Yates, Nicole L. ^{[1
,2
]}

Shen, Xiaoying ^{[1
,2
]}

Koup, Richard A. ^{[9
]}

Pitisuttithum, Punnee ^{[13
]}

Kaewkungwal, Jaranit ^{[13
]}

Nitayaphan, Sorachai ^{[11
]}

Rerks-Ngarm, Supachai ^{[14
]}

Michael, Nelson L. ^{[8
]}

Kim, Jerome H. ^{[8
]}

机构：

[1] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA

[2] Duke Univ, Sch Med, Ctr HIV AIDS Vaccine Immunol, Durham, NC 27710 USA

[3] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA

[4] Fred Hutchinson Canc Res Ctr, Div Clin Res, Vaccine & Infect Dis Div, Seattle, WA 98104 USA

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

[6] NYU, Sch Med, Dept Pathol, New York, NY USA

[7] Harvard Univ, Sch Med, New England Reg Primate Ctr, Dept Microbiol & Immunobiol, Southborough, MA 01772 USA

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

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

[10] Armed Forces Res Inst Med Sci, US Army Component, Bangkok 10400, Thailand

[11] Armed Forces Res Inst Med Sci, Royal Thai Army, Bangkok 10400, Thailand

[12] Siriraj Hosp, Dept Microbiol, Natl HIV Repository & Bioinformat Ctr, Bangkok, Thailand

[13] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand

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

[15] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[16] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[17] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2012年 / 366卷 / 14期

关键词：

DEPENDENT CELLULAR CYTOTOXICITY; IMMUNODEFICIENCY-VIRUS; V1/V2; DOMAIN; ANTIBODY; PROTECTION; INFECTION; RESPONSES; SIV; NEUTRALIZATION; CHALLENGE;

D O I：

10.1056/NEJMoa1113425

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. RESULTS Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P = 0.02; q = 0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P = 0.03; q = 0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies. CONCLUSIONS This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.

引用

页码：1275 / 1286

页数：12

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