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.

Original publication

DOI

10.1073/pnas.1519690113

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

16/02/2016

Volume

113

Pages

1853 - 1858

Keywords

MF59, adjuvant, children, influenza vaccine, systems biology, Adjuvants, Immunologic, Antibodies, Viral, B-Lymphocytes, Humans, Immunologic Memory, Infant, Influenza Vaccines, Polysorbates, Squalene, Systems Biology, Transcriptome