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PMID: 21743478 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Systems biology of vaccination for seasonal influenza in humans.

Nature immunology ·Vol. 12 ·No. 8 ·2011-07-10 ·Pages 786-95

Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B

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.

MeSH Terms
Adaptive Immunity/immunology Adolescent Adult Animals Antibodies, Viral/blood Gene Expression Profiling Hemagglutination Inhibition Tests Humans Immunity, Innate/immunology Influenza Vaccines/administration & dosage,immunology Influenza, Human/immunology,prevention & control Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Orthomyxoviridae/immunology Seasons Systems Biology/methods Vaccination/methods Vaccines, Attenuated/administration & dosage,immunology Vaccines, Inactivated/administration & dosage,immunology Young Adult
Chemicals
Antibodies, Viral Influenza Vaccines Vaccines, Attenuated Vaccines, Inactivated
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Nakaya Helder I
Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
Wrammert Jens
Lee Eva K
Racioppi Luigi
Marie-Kunze Stephanie
Haining W Nicholas
Means Anthony R
Kasturi Sudhir P
Khan Nooruddin
Li Gui-Mei
McCausland Megan
Kanchan Vibhu
Kokko Kenneth E
Li Shuzhao
Elbein Rivka
Mehta Aneesh K
Aderem Alan
Subbarao Kanta
Ahmed Rafi
Pulendran Bali
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2067
Published
2011-07-10
Epub
2011-00-10
Pages
786-95
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3140559
Subset
IM
Grants
NIAID NIH HHS · N01AI50025 · United States
NIAID NIH HHS · U19AI090023 · United States
NIDDK NIH HHS · R01DK057665 · United States
NIAID NIH HHS · U19 AI057266-08 · United States
NIDDK NIH HHS · R01 DK057665-13 · United States
NIAID NIH HHS · U54AI057157 · United States
NIAID NIH HHS · N01AI30048 · United States
NIAID NIH HHS · U19 AI057266-09 · United States
NCATS NIH HHS · UL1 TR000454 · United States
NIGMS NIH HHS · R01 GM033976 · United States
NIAID NIH HHS · R37 AI048638-11 · United States
NIAID NIH HHS · R37AI48638 · United States
NCRR NIH HHS · UL1 RR025008 · United States
NIAID NIH HHS · U19 AI090023-02 · United States
NIAID NIH HHS · AI057266 · United States
NIAID NIH HHS · R37 AI048638 · United States
NIAID NIH HHS · HHSN266200700006C · United States
NIAID NIH HHS · R38 AI140299 · United States
NIDDK NIH HHS · R01 DK057665-12 · United States
NIAID NIH HHS · U19 AI090023 · United States
NIDDK NIH HHS · R01 DK074701 · United States
NIAID NIH HHS · U19 AI057266 · United States
NIAID NIH HHS · U19 AI090023-01 · United States
NIDDK NIH HHS · R01 DK057665 · United States
NIAID NIH HHS · U19AI057266 · United States
NIDDK NIH HHS · R37 DK057665 · United States
NIAID NIH HHS · R37 AI048638-12 · United States
NIAID NIH HHS · AI30048 · United States
NIDDK NIH HHS · DK074701 · United States
NIAID NIH HHS · N01 AI50025 · United States
NIAID NIH HHS · U54 AI057157 · United States
Databases
GEO
GSE29619
Corrections
CommentIn
PMID: 21772284
External Links
PubMed source DOI: 10.1038/ni.2067 PMC Full Text View journal details
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