Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

被引：292

作者：

Chung, Amy W. ^{[1
,2
]}

Kumar, Manu P. ^{[3
]}

Arnold, Kelly B. ^{[3
]}

Yu, Wen Han ^{[1
,3
]}

Schoen, Matthew K. ^{[1
]}

Dunphy, Laura J. ^{[3
]}

Suscovich, Todd J. ^{[1
]}

Frahm, Nicole ^{[4
]}

Linde, Caitlyn ^{[1
]}

Mahan, Alison E. ^{[1
]}

Hoffner, Michelle ^{[1
]}

Streeck, Hendrik ^{[5
,6
]}

Ackerman, Margaret E. ^{[7
]}

McElrath, M. Juliana ^{[4
]}

Schuitemaker, Hanneke ^{[8
]}

Pau, Maria G. ^{[8
]}

Baden, Lindsey R. ^{[1
,9
]}

Kim, Jerome H. ^{[5
,10
]}

Michael, Nelson L. ^{[5
]}

Barouch, Dan H. ^{[1
,11
]}

Lauffenburger, Douglas A. ^{[3
]}

Alter, Galit ^{[1
]}

机构：

[1] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[2] Univ Melbourne, Peter Doherty Inst, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia

[3] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[4] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

[5] US Mil HIV Res Program, Dept Mol Virol & Pathogenesis, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA

[6] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Biol, D-45141 Essen, Germany

[7] Thayer Sch Engn Dartmouth, Hanover, NH 03755 USA

[8] Crucell Holland BV, NL-2333 Leiden, Netherlands

[9] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02215 USA

[10] Int Vaccine Inst, Seoul 151742, South Korea

[11] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

来源：

CELL | 2015年 / 163卷 / 04期

关键词：

EBOLA-VIRUS INFECTION; PROTECTIVE EFFICACY; NEONATAL MICE; ANTIBODY; IGA; CHALLENGES; BINDING; REGION; SERUM;

D O I：

10.1016/j.cell.2015.10.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activitymay help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case: control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

引用

页码：988 / 998

页数：11

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