Evaluating mRNA-Based Vaccines Against Burkholderia pseudomallei 9252

Abstract Description Burkholderia pseudomallei, the etiologic agent of melioidosis, is an emerging pathogen present in soil and water in tropical regions around the world. Two key protective antigens have been identified and successfully used to ameliorate disease in rodent models of pneumonic melioidosis in conjugate subunit vaccines: capsular polysaccharide (CPS) and the protein antigen Hcp1. We evaluated the ability of conventional and self-amplifying mRNA-based lipid nanoparticle (LNP) vaccines to elicit immune responses in C57BL/6 mice. Animals were vaccinated at day 0 and 28 with either Hcp1-mRNA:LNP alone or in combination with CPS conjugate adjuvanted with CpG 2006 and Alhydrogel. Immune responses were compared to animals vaccinated with the conjugate subunit vaccine and negative controls. Humoral and cell-mediated immune responses were assessed at 7-days post-boost. Conventional mRNA-based constructs elicit minimal immune responses against Hcp1 compared to the conjugate subunit vaccine, both in terms of antibody titer and T-cell responses, while the self-amplifying mRNA vaccine induced more robust responses. Hcp1 responses were enhanced in animals that received both mRNA and adjuvanted conjugate vaccines, compared to mRNA alone, suggesting that adjuvant may have an important role in enhancing the immunogenicity of mRNA-based vaccines. Additional optimization in mRNA design and in vivo expression are likely needed to achieve efficacy of current subunit-based vaccine formulations. Topic Categories Vaccines and Immunotherapy (VAC)