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Cell. 2017 May 18;169(5):862-877.e17. doi: 10.1016/j.cell.2017.04.026. Epub 2017 May 11.

Metabolic Phenotypes of Response to Vaccination in Humans.

Author information

1
Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30303, USA.
2
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
3
Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30303, USA; Hope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
4
Department of Bioinformatics and Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA 30030, USA.
5
University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
6
Department of Infectious Diseases and Vaccines-West Point, PA, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
7
Department of Bioengineering, Department of Chemistry and Biochemistry, Department of Nanoengineering, Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
8
Division of Vaccine Discovery, La Jolla Institute of Immunology, La Jolla, CA 92037, USA.
9
School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508, Brazil; Department of Pathology, School of Medicine, Emory University, Atlanta, GA 30329, USA.
10
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
11
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA; Department of Pathology, School of Medicine, Emory University, Atlanta, GA 30329, USA. Electronic address: bpulend@emory.edu.

Abstract

Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

KEYWORDS:

Zostavax; herpes zoster vaccine; immune response; metabolomics; multiscale; shingles; systems biology; transcriptomics

PMID:
28502771
PMCID:
PMC5711477
DOI:
10.1016/j.cell.2017.04.026
[Indexed for MEDLINE]
Free PMC Article

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