A vaccine platform that promotes Fc-dependent effector functions by recruiting helper T cells induced by prior BCG immunization 2990

Abstract Description Antibodies are effective against many diseases ranging from viral infections to tumors. The quality of CD4+ T (Th) cells is of importance in the development of these protective antibodies. Here, we designed a vaccine platform that uses BCG specific Th cells to drive anti-Ebola virus (EBOV) antibody responses. BCG Th cells are abundant in BCG vaccinated individuals, including those who reside in EBOV endemic regions. To recruit pre-existing BCG Th cells to promote anti-EBOV antibody responses, a vaccine (P25-EBOV GP) was developed that consists of the EBOV GP fused to the mycobacteria Th cell epitope (P25) of Ag85B. Presentation of the P25 epitope by B cells recruited cognate interactions with P25-specific Th cells to promote anti-EBOV GP antibody responses. Experiments in mice showed the induction of IgG2c antibodies only occurred in BCG primed mice, consistent with BCG vaccination as a known inducer of Th1 responses that drive class-switching to this isotype. Furthermore, BCG vaccination induced strong FcgR expression on effector cells such as neutrophils, macrophages, and NK cells, further enhancing the effector activities of these antibodies. Eliciting the IgG2c subclass of anti-EBOV GP antibodies by our P25-EBOV GP vaccine protected mice against lethal EBOV infection. Taking advantage of prior BCG immunization, this vaccine platform can be easily adapted to target other viral immunogens as well as tumor antigens to induce antibodies with Fc-dependent effector functions. Funding Sources NIH 5R01AI045889-24; Intramural Research Program, NIAID Topic Categories Vaccines and Immunotherapy (VAC)