Metabolic Phenotypes of Response to Vaccination in Humans

Publication date: Available online 11 May 2017
Source:Cell
Author(s): Shuzhao Li, Nicole L. Sullivan, Nadine Rouphael, Tianwei Yu, Sophia Banton, Mohan S. Maddur, Megan McCausland, Christopher Chiu, Jennifer Canniff, Sheri Dubey, Ken Liu, ViLinh Tran, Thomas Hagan, Sai Duraisingham, Andreas Wieland, Aneesh K. Mehta, Jennifer A. Whitaker, Shankar Subramaniam, Dean P. Jones, Alessandro Sette, Kalpit Vora, Adriana Weinberg, Mark J. Mulligan, Helder I. Nakaya, Myron Levin, Rafi Ahmed, Bali Pulendran
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.

Graphical abstract

Teaser

An integrated metabolic response underlies the immune response to shingles vaccine in humans.


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