Transcriptional profiling of immunity to the MF-59 – adjuvanted influenza vaccine in children

In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15-24 months old) and in young healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. The pediatric population is a major target of vaccination, yet there is a paucity of studies on the transcriptional response of immunity to vaccination in this special population. In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15-24 months old) and in young healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. Our analysis revealed that primary vaccination induced a persistent transcriptional signature of innate immunity; booster vaccination induced a transcriptional signature of an enhanced memory-like innate response, which was consistent with enhanced activation of myeloid cells assessed by FACS. Furthermore, we identified a transcriptional signature of type 1 IFN response post booster vaccination and at baseline that was correlated with the local reactogenicity to vaccination, and defined an early signature of the hemagglutinin antibody titers. These results highlight an adaptive behavior of the innate immune system in evoking a memory-like response to secondary vaccination and define molecular correlates of reactogenicity and immunogenicity in infants. 90 children, aged 15 to 24 months, were randomized into three cohorts. Each participant received two doses of seasonal TIV vaccine with MF59 adjuvant, 28 days apart. Peripheral blood was collected. Due to the limitations on the number of blood draws that could be obtained from a child, we utilized a staggered sample collection design. Pre-vaccination baseline samples were obtained from individuals in cohort A. Pre-boost baseline samples were obtained from those in cohorts B and C. Children in Cohort A were sampled also at Day 1 post primary vaccination. Children in cohorts B and C were sampled at Day 1 and Day 3 post boost vaccination, respectively. Blood was also collected from all subjects 28 days after the boost vaccination to access the serological responses. Thirty young healthy adult volunteers (cohort D) received a single ATIV injection, and blood was collected from all adult subjects prior to vaccination, and at days 1, 3 and 28 post vaccination.