Differential effects of adjuvants on shaping unique B cell responses in a dose-sparing seasonal influenza vaccine 4246

Abstract Description Adjuvants enhance the magnitude and durability of antibody-mediated immunity to vaccines, even with lower doses of antigen. However, limited studies have directly compared how different adjuvants might influence immune responses elicited under such dose-sparing regimens. Here, we investigate three different adjuvants in mice—AddaVax (MF59-like), IMDQ-PC (TLR7/8 agonist), and IMDQ-PC complimented with SDI (RIG-I agonist)—for their capacity to promote effective antibody-mediated immunity when combined with a dose-sparing quantity of quadrivalent inactivated influenza vaccine (QIV). We found that each adjuvant displayed a unique immune response skewing that correlated with protection during infection. AddaVax displayed a Th2 biased response in contrast to IMDQ-PC and IMDQ-PC+SDI’s observed Th1 bias. All three adjuvants induced substantial germinal center B cell (GCBC) responses in the draining lymph nodes (dLNs), however only IMDQ-PC vaccines displayed significant immune response in the spleen (SP). Consistent with GCBC kinetics, CD4+ follicular helper T cells were also highly expanded in adjuvant immunized mice. IMDQ-PC vaccines also appeared to more favorably promote extrafollicular B cell response with markedly increased numbers of early plasmablasts and an activated memory precursors population in both the dLNs and SPs. Similarly, IMDQ-PC vaccines showed a significant increase in swIg CD80+ PD-L2+ memory B cells which are thought to be primarily GC-derived. Funding Sources Supported by T32AI007647 awarded to M.J.P.; NIH/NIAID R21AI151229; R21AI176069; R44AI176894; CEIRR contract number 75N93021C00014; and by NIAID SEM-CIVIC contract number 75N93019C00051. Topic Categories Vaccines and Immunotherapy (VAC)