title: Systems biology of vaccination for seasonal influenza in humans.
abstract: Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.
authors: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
authors: Helder I
authors: HI
authors: Nakaya
authors: Jens
authors: J
authors: Wrammert
authors: Eva K
authors: EK
authors: Lee
authors: Luigi
authors: L
authors: Racioppi
authors: Stephanie
authors: S
authors: Marie-Kunze
authors: W Nicholas
authors: WN
authors: Haining
authors: Anthony R
authors: AR
authors: Means
authors: Sudhir P
authors: SP
authors: Kasturi
authors: Nooruddin
authors: N
authors: Khan
authors: Gui-Mei
authors: GM
authors: Li
authors: Megan
authors: M
authors: McCausland
authors: Vibhu
authors: V
authors: Kanchan
authors: Kenneth E
authors: KE
authors: Kokko
authors: Shuzhao
authors: S
authors: Li
authors: Rivka
authors: R
authors: Elbein
authors: Aneesh K
authors: AK
authors: Mehta
authors: Alan
authors: A
authors: Aderem
authors: Kanta
authors: K
authors: Subbarao
authors: Rafi
authors: R
authors: Ahmed
authors: Bali
authors: B
authors: Pulendran
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D020869:Gene Expression Profiling; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology*; D012621:Seasons; D049490:Systems Biology / Q000379:methods; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated