The effectiveness and immunogenicity of an oil-in-water nano-emulsion protein subunit vaccine against Pseudomonas aeruginosa in diet induced obese mice 2193

Abstract Description Pseudomonas aeruginosa (Pa) is an opportunistic pathogen known to cause severe infections of upper and/or lower respiratory tracts in immunocompromised individuals. With 13% of the world’s population being obese, infections and immunesenescence are on the rise. Moreover, increased fitness of Pa is conferred by the absence of licensed vaccines, rising antibiotic resistance to name a few. We showed LTA-1 fused type three secretion system associated proteins of Pa, PcrV and PopB (L-PaF) in oil-in-water nano-emulsion ME to be protective in young and elderly mice in presence and absence of TLR agonist BECC438b. Here, we extended our work in the realm of obese mice where dose-escalation studies using L-PaF were found to be reducing the onset of infection. Optimum concentration of the immunogen was established by checking humoral, cellular responses before and after immunization and lung burden post infection. Correlates of protection were established in terms of presence of antibodies with high opsonophagocytic activity, IL-17A and IFN-g in spleens and IL-22, IL-17A and IL-2 in lungs before challenge. Challenge with mucoid Pa clinical isolate, however, changes the cytokine signature into a more pro-inflammatory type in lungs, compared to spleen in control vs immunized mice. This work addresses a serious health risk and shows a way to prevent it. Funding Sources This work was funded by the U.S. Department of Health & Human Services (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to WLP (grant number: R01AI169781), and by the U.S. Department of Health & Human Services (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to RKE (contract number: HHSN272201800043C). Topic Categories Vaccines and Immunotherapy (VAC)