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Cell. 2015 Nov 5;163(4):988-98. doi: 10.1016/j.cell.2015.10.027.

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

Author information

1
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia.
2
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
5
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
6
Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA; Institute for Medical Biology, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany.
7
Thayer School of Engineering at Dartmouth, Hanover, NH 03755, USA.
8
Crucell Holland B.V., The Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden 2333, the Netherlands.
9
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02215, USA.
10
Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA; International Vaccine Institute, Seoul 151-742, Republic of Korea.
11
Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA.
12
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
13
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: lauffen@mit.edu.
14
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.

Abstract

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.

PMID:
26544943
PMCID:
PMC5490491
DOI:
10.1016/j.cell.2015.10.027
[Indexed for MEDLINE]
Free PMC Article

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