Metabolic Phenotypes Of Response to Vaccination in Humans

• Type of Material: Article
• Authors: Shuzhao Li, Emory University; Nicole L. Sullivan, Yerkes National Primate Research Center; Nadine Rouphael, Emory University; Tianwei Yu, Emory University; Sophia Banton, Emory University; Mohan S. Maddur, Yerkes National Primate Research Center; Megan McCausland, Yerkes National Primate Research Center; Christopher Chiu, Yerkes National Primate Research Center; Jennifer Canniff, University of Colorado; Sheri Dubey, Merck & Co., Inc.; Ken Liu, Emory University; ViLinh Tran, Emory University; Thomas Hagan, Yerkes National Primate Research Center; Sai Duraisingham, Yerkes National Primate Research Center; Andreas Wieland, Yerkes National Primate Research Center; Aneesh K Mehta, Emory University; Jennifer A. Whitaker, Emory University; Shankar Subramaniam, University of California at San Diego; Dean P Jones, Emory University; Alessandro Sette, La Jolla Institute for Allergy and Immunology; Kalpit Vora, Merck & Co., Inc.; Adriana Weinberg, University of Colorado; Mark Mulligan, Emory University; Helder Nakaya, Emory University; Myron Levin, University of Colorado; Rafi Ahmed, Emory University; Bali Pulendran, Emory University
• Language: English
• Date: 2017-05-18
• Publisher: IOS Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2017.04.026
• Title of Journal or Parent Work: Analytical Cellular Pathology / Cellular Oncology
• ISSN: 1570-5870
• Volume: 169
• Issue: 5
• Start Page: 862
• End Page: +
• Grant/Funding Information: This work was supported by NIH grants U19AI090023 (B.P.), U19AI057266 (R.A. and B.P.).
• Keywords: Biochemistry & Molecular Biology; YELLOW-FEVER VACCINE; GENE-EXPRESSION; SYSTEMS BIOLOGY; ACTIVATION; VARICELLA-ZOSTER-VIRUS; Cell Biology; IMMUNOLOGY; Life Sciences & Biomedicine; MACROPHAGES; Science & Technology; INNATE; SEASONAL INFLUENZA; IMMUNE CELL-FUNCTION
• Research Categories: Health Sciences, Pathology; Biology, Biostatistics; Chemistry, Biochemistry

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.