Development of Single-Administration Burkholderia pseudomallei Vaccines using Atomic Layering Thermostable Antigen and Adjuvant (ALTA®) Technology 2259779

Abstract

Abstract Introduction Melioidosis, an infectious disease caused by Burkholderia pseudomallei (Bp), is difficult to treat due to intrinsic antibiotic resistance, latency with subsequent recrudescence and a diverse non-specific symptomatology. A vaccine is needed to effectively control this disease burden around the globe. Here we tested the efficacy of a novel Bp vaccine containing hemolysin-coregulated protein (Hcp1), capsular polysaccharide (CPS)-CRM197 conjugate, and CpG using the Atomic Layering Thermostable Antigen and Adjuvant (ALTA®) platform. Methods C57BL/6 mice were vaccinated and the protective efficacy as well as immunological profiles were evaluated pre- and post-aerosol challenge with B. pseudomallei K96243 strain. Results Each tested dose of Bp ALTA® formulation demonstrated protective efficacy (20-50%) over a non-vaccinated control. Mechanistically, the Bp ALTA® formulations increased Hcp1-directed IFN-gamma recall in splenocytes, and produced robust antibody response against the principal dominant antigen, CPS. High levels of anti-CPS antibodies were associated with significant decrease in bacterial burden in the lung. Conclusion The ALTA® platform, which has previously been shown to provide antigen thermostability, was utilized in this study for Bp vaccination achieving protective efficacy from a single-shot administration. Studies are ongoing to optimize the immunogenic potential and protective capacity of these novel formulations. Funding Source DTRA-JSTO Topic Categories Vaccines and Immunotherapy (VAC)