title: Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
abstract: Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, São Paulo 05508, Brazil; Department of Pathology, School of Medicine, Emory University, 1648 Pierce Drive NE, Atlanta, GA 30307, USA.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Department of Bioengineering, University of California, 9500 Gilman Drive MC 0412, San Diego, La Jolla, CA 92093, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hagan
authors.affiliation: Department of Immunology, Churchill Hospital, Oxford University Hospitals NHS Trust, Old Road, Oxford OX3 7J, UK.
authors.forename: Sai S
authors.initials: SS
authors.lastname: Duraisingham
authors.affiliation: Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, North Avenue NW, Atlanta, GA 30332, USA.
authors.forename: Eva K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Institute for Molecular Engineering, University of Chicago, 5640 S. Elis Avenue, Chicago, IL 60637, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kwissa
authors.affiliation: Hope Clinic of Emory University, 500 Irvin Court/Suite 200, Atlanta, GA 30030, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rouphael
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frasca
authors.affiliation: Department of Bioengineering, University of California, 9500 Gilman Drive MC 0412, San Diego, La Jolla, CA 92093, USA.
authors.forename: Merril
authors.initials: M
authors.lastname: Gersten
authors.affiliation: Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, 1648 Pierce Drive NE, Atlanta, GA 30307, USA.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Department of Immunology, Faculty of Medicine, Technion, 1 Efron Street, Haifa 3109601, Israel.
authors.forename: Renaud
authors.initials: R
authors.lastname: Gaujoux
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Gui-Mei
authors.initials: GM
authors.lastname: Li
authors.affiliation: Department of Bioengineering, University of California, 9500 Gilman Drive MC 0412, San Diego, La Jolla, CA 92093, USA.
authors.forename: Shakti
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Microbiology and Immunology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA; Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Hope Clinic of Emory University, 500 Irvin Court/Suite 200, Atlanta, GA 30030, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Department of Immunology, Faculty of Medicine, Technion, 1 Efron Street, Haifa 3109601, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Shen-Orr
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA.
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
authors.affiliation: Department of Bioengineering, University of California, 9500 Gilman Drive MC 0412, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA 92093, USA; Department of Nanoengineering, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA 92093, USA; Department of Computer Science and Engineering, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA 92093, USA. Electronic address: shankar@ucsd.edu.
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Department of Pathology, School of Medicine, Emory University, 1648 Pierce Drive NE, Atlanta, GA 30307, USA; Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA. Electronic address: bpulend@emory.edu.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012621:Seasons; D013597:Systems Analysis; D059467:Transcriptome / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines