Systems biology of vaccination for seasonal influenza in humans

Abstract

We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines.

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

“…Several recent studies have focused on characterizing the early phase of the immune response in the first days (days 1‐3) after influenza vaccination 17, 18, 19. RNA‐seq profiling identified gene expression patterns predictive of immunogenicity17 and adverse events 18.…”

“…RNA‐seq profiling identified gene expression patterns predictive of immunogenicity17 and adverse events 18. Meanwhile, another report identified a correlation between injection site soreness and serum cytokines 1‐2 days after receiving TIV in healthy pregnant and non‐pregnant women 19…”

“…Recently, systems biology approaches have been used to prospectively explore the molecular determinants of influenza vaccine responses including efficacy and/or adverse events 17, 18. Although different vaccines were used, both of these studies identified early immune gene expression signatures (1‐3 days after immunization) which predicted immunogenicity17 and the onset of clinical adverse events 18…”

“…Although different vaccines were used, both of these studies identified early immune gene expression signatures (1‐3 days after immunization) which predicted immunogenicity17 and the onset of clinical adverse events 18…”

Drug development: Searching for patterns

“…Pulendran's team has used systems biology to assess the seasonal influenza vaccine for any signatures that might predict an antibody response 5 . The team compared two flu vaccines -a trivalent inactivated vaccine and a live attenuated vaccine -and found signatures that predicted the human antibody response to the vaccine.…”