Vaccination Consolidation: Dual-Engineered Vaccine Confers Protection against Yersinia pestis and Burkholderia pseudomallei Aerosol Challenge 2259579

Abstract

Abstract Introduction Yersinia pestis (Yp) and Burkholderia pseudomallei (Bp), the causative agents of plague and melioidosis respectively, are both responsible for extremely high lethality. There are no FDA-approved vaccines against these pathogens, and treatments are challenging due to antibiotic resistance. Methods Here we developed a multi-pathogen vaccine against Yp and Bp. Mice were vaccinated with a nanolipoprotein (NLP) formulated with Yp Fraction 1 protein (F1), Yp low calcium response V protein (V), Bp hemolysin-coregulated protein 1 (Hcp1) as well as Bp capsular polysaccharide (CPS) admixed with CpG and aluminum hydroxide wet gel (AlOH), following a two-dose vaccine schedule. We used a model of pneumonic plague and melioidosis in which C57BL/6 mice were initially aerosol challenged with Yp, and following convalescence mice were then challenged with Bp. Results The multi-pathogen vaccine conferred 100% and 60% protection following Yp and Bp challenge, respectively. Anti-F1, -V, and -Hcp1 IgG titers in serum reached similar levels between all vaccine groups and appeared to diminish at a similar rate. The magnitude of the IFN-gamma recall response of splenocytes was less pronounced in the multi-pathogen vaccine, although it conferred similar protection as current benchmark vaccines. Conclusion The multi-pathogen vaccine was comparably protective to benchmark vaccines but with the advantage of reduced number of injections and dose sparing. These data show that the NLP platform is amenable to multi-pathogen formulations and a single vaccine regimen can protect from both pneumonic plague and melioidosis. Funding Source DTRA-JSTO Topic Categories Vaccines and Immunotherapy (VAC)