Journal
NATURE IMMUNOLOGY
Volume 12, Issue 8, Pages 786-U149Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2067
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Funding
- US National Institutes of Health [U19AI090023, HHSN266200700006C, U54AI057157, R37AI48638, R01DK057665, U19AI057266, N01 AI50025, AI30048, AI057266, DK074701, UL1 RR025008]
- Bill & Melinda Gates Foundation [38645]
- National Science Foundation (E.K.L. laboratory)
- Centers for Disease Control (E.K.L. laboratory)
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [800057] Funding Source: National Science Foundation
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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.
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