title: Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood.
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.
authors.affiliation: 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;
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: 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;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Clutterbuck
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329;
authors.forename: Dmitri
authors.initials: D
authors.lastname: Kazmin
authors.affiliation: Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom;
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329;
authors.forename: Mario
authors.initials: M
authors.lastname: Cortese
authors.affiliation: 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;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: Division of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30322;
authors.forename: Nirav B
authors.initials: NB
authors.lastname: Patel
authors.affiliation: Center for Infectious Disease Research, Seattle, WA 98109;
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Zak
authors.affiliation: Center for Infectious Disease Research, Seattle, WA 98109;
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.affiliation: Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom;
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.affiliation: Research Center, Novartis Vaccines, 53100 Siena, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.affiliation: Research Center, Novartis Vaccines, 53100 Siena, Italy; rino.r.rappuoli@gsk.com bpulend@emory.edu Claire-Anne.Siegrist@unige.ch.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Medical Research Council Human Immunology Unit, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom;
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.affiliation: 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;
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: 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.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.affiliation: 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.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage*; D049490:Systems Biology; D059467:Transcriptome
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: MF59; adjuvant; children; influenza vaccine; systems biology