Vaccine adjuvants instruct antibody durability and secretory capacity of antibody secreting cells following immunization 4367

Abstract Description Durable antibody responses are a critical feature of successful vaccines; however, durability varies widely, largely based on the immunogen and adjuvant used. The ideal combination of triggers and inflammation necessary to promote durable immunity remains unknown. In this study, we immunized C57BL/6 mice with two-doses of either SARS-CoV-2 mRNA or Spike S1 recombinant protein adjuvanted with SLA-LSQ (28 days apart). Antibody titers (binding and neutralizing) were measured overtime. Both vaccines elicited a robust and durable antibody response. At endpoint (6 months), ELISpots were performed to quantify number and size of Spike-specific spots from bone marrow derived plasma cells. Interestingly, differences in spot size, but not number, were observed between groups. To follow up on this observation, C57BL/6 mice were vaccinated with model antigen (NP-CGG) + a panel of adjuvants (empty lipid nanoparticles, Alhydrogel, AddaS03, or Quil-A) and ELISpot size differences were quantified. Quil-A, a saponin-based adjuvant, resulted in significantly larger antigen-specific bone marrow derived spots compared to other adjuvants tested. These data support the claim that differences in the secretory capacity of long-lived plasma cells are programed early during an immune response and are adjuvant dependent. This could have profound impacts on the durability and breadth of antibody responses elicited by vaccination. Funding Sources Supported by NIH/NIAID R01AI1229945 (DB), Bill and Melinda Gates Foundation INV-051356 (DB), and BIO5 Postdoctoral Fellowship (ZL). Topic Categories Vaccines and Immunotherapy (VAC)