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Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1853-8. doi: 10.1073/pnas.1519690113. Epub 2016 Jan 11.

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

Author information

1
Department of Pathophysiology and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, 05508, São Paulo, Brazil; Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322;
2
Oxford Vaccine Group, Department of Pediatrics, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre, Oxford OX3 9DU, United Kingdom;
3
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329;
4
Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom;
5
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329; Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322;
6
Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322;
7
Center for Infectious Disease Research, Seattle, WA 98109;
8
Research Center, Novartis Vaccines, 53100 Siena, Italy;
9
Research Center, Novartis Vaccines, 53100 Siena, Italy; rino.r.rappuoli@gsk.com bpulend@emory.edu Claire-Anne.Siegrist@unige.ch.
10
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322; Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329; rino.r.rappuoli@gsk.com bpulend@emory.edu Claire-Anne.Siegrist@unige.ch.
11
WHO Collaborative Center for Vaccine Immunology, Departments of Pathology-Immunology and Pediatrics, University of Geneva, 1211 Geneva, Switzerland rino.r.rappuoli@gsk.com bpulend@emory.edu Claire-Anne.Siegrist@unige.ch.

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.

KEYWORDS:

MF59; adjuvant; children; influenza vaccine; systems biology

Comment in

PMID:
26755593
PMCID:
PMC4763735
DOI:
10.1073/pnas.1519690113
[Indexed for MEDLINE]
Free PMC Article

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