Vaccine adjuvant choice regulates antigen-specific B cell activation and phenotype

Abstract

Abstract There has been a global rise of antibiotic resistant bacteria that are causing a significant increase in morbidity and mortality. Vaccines offer one of the best ways to combat and prevent these infections. Antibody responses are often the most effective outcomes of vaccine-induced immunity; however, the role of different vaccine adjuvants has not been fully explored in terms of antigen-specific B cell responses. Using a B cell antigen tetramer, we sought to determine how a novel adjuvant, double mutant heat labile toxin from enterotoxigenic E. Coli (dmLT), compared with those currently used in vaccines. We show that either intradermal or intramuscular immunization of mice with a model vaccine formulated using dmLT induces greater antigen specific B cell numbers in the injection site draining lymph nodes and spleen compared to antigen alone. These B cells were also antibody isotype switched and were phenotypically germinal center B cells. We further demonstrate that vaccine-specific B cells migrate from the injection site draining lymph nodes to more distal lymphoid organs. When we compared dmLT to the most commonly used human vaccine adjuvant, alum, we found dmLT was better at inducing a B cell response. Lastly, we show that dmLT is a more potent B cell adjuvant compared to the TLR4 agonist monophosphoryl lipid A (MPL-A) and that the combination of these two adjuvants is superior to either adjuvant alone. Interestingly, MPL-A induced greater antigen specific IgG compared to dmLT despite dmLT inducing a more robust B cell expansion. These results demonstrate that dmLT is a potent B cell activating adjuvant and that combining dmLT with existing adjuvants has the potential to greatly improve vaccine responses.