Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood.

TitleSystems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood.
Publication TypeJournal Article
Year of Publication2016
AuthorsNakaya HI, Clutterbuck E, Kazmin D, Wang L, Cortese M, Bosinger SE, Patel NB, Zak DE, Aderem A, Dong T, Del Giudice G, Rappuoli R, Cerundolo V, Pollard AJ, Pulendran B, Siegrist C-A
JournalProc Natl Acad Sci U S A
Volume113
Issue7
Pagination1853-8
Date Published02/16/2016
ISSN1091-6490
Abstract

The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.

DOI10.1073/pnas.1519690113
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID26755593
PubMed Central IDPMC4763735
Grant ListAI100663-02 / AI / NIAID NIH HHS / United States
G1000800 / / Medical Research Council / United Kingdom
MC_UU_12010/1 / / Medical Research Council / United Kingdom
R37AI48638 / AI / NIAID NIH HHS / United States
R37DK057665 / DK / NIDDK NIH HHS / United States
U19 AI090023 / AI / NIAID NIH HHS / United States
U19AI057266 / AI / NIAID NIH HHS / United States
U19AI090023 / AI / NIAID NIH HHS / United States
/ / Medical Research Council / United Kingdom
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