Genetic analysis of differential responses to adjuvanted influenza vaccination

Abstract

Abstract Each year the seasonal influenza vaccine is administered to protect individuals from infection, but vaccination often shows variable efficacy against influenza infections. While the inclusion of adjuvants can boost vaccine efficacy, individuals also vary in their response to adjuvants, and understanding the basis of this variation would provide insights into adjuvant mechanisms and advance vaccine development. Host genetics contribute to variation in vaccine response, but the specific genetic factors that impact immune responses to adjuvanted vaccination are not well understood. To better understand how the genetic background of individuals can modify vaccine and adjuvant-induced immune responses, we screened a set of Collaborative Cross (CC) mouse strains with immunization via inactivated influenza with or without alum. Across these genetically diverse CC strains, we observed wide variation in levels of influenza specific antibodies and isotypes (e.g., IgG1, IgG2). We further focused on two strains, CC002 and CC072, that had contrasting antibody responses to vaccine + alum. To understand the genetic factors driving these responses, we generated an F2 population to map quantitative trait loci (qtl) driving the differences between CC002 and CC072 in vaccine responses. Among the F2 population, variation across antibody levels were observed in mice vaccinated with the vaccine with and without alum that reflected the variation in the parent strains. QTL were mapped for variation in antibody levels for mice vaccinated without alum, further supporting a role for host genetics in regulating vaccine responses. Future analysis will focus on analyzing specific host factors modulating antibody responses to adjuvanted vaccination. Supported by grants from NIH (U19 AI100625, 5T32 GM007092, 1T32 GM135128, 5R25 GM055336-19) and Burroughs Wellcome Fund GDEP to MCC.