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

Amy W. Chung, Manu P. Kumar, Kelly B. Arnold, Wen Han Yu, Matthew K. Schoen, Laura J. Dunphy, Todd J. Suscovich, Nicole Frahm, Caitlyn Linde, Alison E. Mahan, Michelle Hoffner, Hendrik Streeck, Margaret E. Ackerman, M. Juliana McElrath, Hanneke Schuitemaker, Maria G. Pau, Lindsey R. Baden, Jerome H. Kim, Nelson L. Michael, Dan H. BarouchDouglas A. Lauffenburger*, Galit Alter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

273 Scopus citations

Abstract

Summary 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 activity may 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.

Original languageEnglish
Pages (from-to)988-998
Number of pages11
JournalCell
Volume163
Issue number4
DOIs
StatePublished - 5 Nov 2015
Externally publishedYes

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