<i>Rickettsia rickettsii</i> inactivated whole cell antigen vaccine protects against Rocky Mountain spotted fever independent of the adjuvant used

Rocky Mountain spotted fever (RMSF) caused by <i>Rickettsia rickettsii</i> is the most fatal tick-borne disease in people and dogs in the Americas. This pathogen is transmitted by several hard ticks: <i>Dermacentor</i> species, <i>Rhipicephalus sanguineus</i>, and <i>Amblyomma americanum</i>. RMSF can quickly progress to a life-threatening illness with fatalities ranging from 30% to 80%. Doxycycline is the only treatment option, and currently, no methods are available to prevent RMSF. We previously reported that vaccination with <i>R. rickettsii</i> whole cell antigen vaccine (WCAV) with Montanide gel adjuvant offers protection against virulent <i>R. rickettsii</i> infection in dogs. Here, we compared three adjuvants to optimize the safety and immunogenicity of WCAV: Alhydrogel, Montanide, and Quil A. Independent of adjuvants, all vaccinees were protected, whereas unvaccinated dogs developed the clinical disease. Vaccination reduced the pathogen to undetectable levels in blood and various tissues. An <i>R. rickettsii-</i>specific IgG response was observed following primary vaccination in all vaccinated groups, which augmented after booster. The vaccine with Quil A had the highest IgG response with a significant rise in CD4⁺ and CD8⁺ T cell numbers, while Montanide and Alhydrogel resulted in a balanced IgG response. IgG2 was the primary antibody detected in unvaccinated infection controls. Several systemic proinflammatory cytokines varied after infection in both vaccinees and controls. Plasma concentration of intercellular adhesion molecule 1 was higher in unvaccinated compared to vaccinees in the first 9 days after infection. This study demonstrates that the WCAV efficacy is independent of the adjuvant, although Quil A induced a higher IgG response and expansion of CD4 and CD8 T cells.