PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/
(Accessed 16 January 2016)

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Biological Sciences – Immunology and Inflammation
Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood
Helder I. Nakaya, Elizabeth Clutterbuck, Dmitri Kazmin, Lili Wang, Mario Cortese, Steven E. Bosinger, Nirav B. Patel, Daniel E. Zak, Alan Aderem, Tao Dong, Giuseppe Del Giudice, Rino Rappuoli, Vincenzo Cerundolo, Andrew J. Pollard, Bali Pulendran, and Claire-Anne Siegrist
PNAS 2016 ; published ahead of print January 11, 2016, doi:10.1073/pnas.1519690113 Author Affiliations
Significance
Vaccines are one of the most cost-effective public health tools in history and offer a means to probe the human immune system. Recent advances have applied the tools of systems biology to study immune responses to vaccination in humans. Here we describe the application of this “systems vaccinology” approach to studying immunity to vaccination of 14- to 24-mo-old children with the inactivated influenza vaccine, administered with or without the MF59 adjuvant. These results reveal important new insights about the dynamics of the innate and adaptive responses to vaccination in this population, and identify potential correlates of immunity to vaccination in children.
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.