Systems biology approach unveils the cellular and molecular mechanisms of formalin-inactivated whole cell vaccine-induced protective immunity against Coxiella burnetii infection in mice

BackgroundThe formalin-inactivated Coxiella burnetii virulent phase I vaccine (PIV) has been shown to be more protective than the avirulent phase II vaccine (PIIV) against virulent C. burnetii challenge in animal models.

However, the cellular and molecular mechanisms underlying the differential ability of PIV and PIIV to induce protective immunity remain unclear.MethodsPIV and PIIV were generated from axenic (ACCM-D) cultures and administered to mice using single or multiple immunization regimens. Protective efficacy was evaluated following challenge with virulent C.

burnetii. Humoral immune responses were assessed by measuring phase I–specific IgM and IgG antibodies.

Bulk RNA sequencing and flow cytometry were used to compare immune responses in PIV- and PIIV-vaccinated mice. The role of neutrophils in vaccine-mediated protection was examined through neutrophil depletion prior to challenge.ResultsRegardless of single or multiple immunizations, PIV and PIIV generated from axenic (ACCM-D) cultures retained their differential protective efficacies, with PIV providing robust protection but PIIV did not.

PIV elicited earlier phase I-specific IgM responses and sustained higher IgG responses compared to PIIV, indicating differences in immunogenicity.