AddaVax-Adjuvanted Inactivated Vaccine Confers Protection Against Listeria monocytogenes Challenge in Mice

Listeria monocytogenes (Lm) is a facultative intracellular pathogen responsible for life-threatening listeriosis, characterized by high mortality rates. Currently, there is no vaccine available for the prevention or treatment of listeriosis. Here, we developed two adjuvanted inactivated vaccines and evaluated their safety, immunogenicity, and protective efficacy. The hypervirulent Lm strain XYSN was inactivated with β-propiolactone (BPL) and formulated with AddaVax or Alum to produce inactivated vaccines (ADIV and ALIV) respectively. Local reactogenicity and histopathological observations revealed no adverse reactions in a murine model. Humoral assays demonstrated both ADIV and ALIV induced higher antibody titers against Lm XYSN, with ADIV eliciting stronger cellular immune responses, as indicated by increased IL-17 and IFN-γ expression in spleen cells. Notably, ADIV conferred 83.3% protection against a lethal challenge with hypervirulent Lm strain, representing a 50% increase compared with the 33.3% protection achieved by ALIV. AddaVax adjuvant not only augmented humoral responses to inactivated bacterial cells but also elicited stronger cellular immune responses compared to Alum adjuvants, resulting in enhanced immune protection. This research offers insights into developing novel inactivated vaccines for listeriosis prevention, particularly beneficial for immunocompromised individuals.