Systems biology of vaccination for seasonal influenza in humans

• Published in: Nature immunology Vol. 12; no. 8; pp. 786 - 795
• Main Authors: Nakaya, Helder I, 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2011; Nature Publishing Group
• Subjects: 631/250/251/1567; 631/250/255/1578; 631/553; Adaptive Immunity - immunology; Adolescent; Adult; Animals; Antibodies; Antibodies, Viral - blood; Antigens; B cells; Biology; Biomedical and Life Sciences; Biomedicine; Biotechnology industries; Ca2+/calmodulin-dependent protein kinase IV; Care and treatment; Clinical trials; Gene expression; Gene Expression Profiling; Genetic aspects; Hemagglutination Inhibition Tests; Humans; Immunity, Innate - immunology; Immunization; Immunogenicity; Immunology; Infectious Diseases; Influenza; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Medical schools; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Orthomyxoviridae - immunology; resource; Seasons; Systems Biology - methods; Vaccination; Vaccination - methods; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; Young Adult; United States
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.2067

Identifying molecular predictors of effective vaccination is an important clinical and technical goal. Pulendran and colleagues use a systems biology approach to study human responses to vaccination against influenza and determine the correlates of immunogenicity. 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.