Coxiella burnetii Nine Mile phase I primary infection derived protective immunity against C. burnetii reinfection in mice depends on both B and T cells, but T cells play a critical role

<i>Coxiella burnetii</i> is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. Acute Q fever is usually a flu-like, self-limiting or treatable illness, but some infections can turn into a severe and sometimes fatal chronic disease. There is currently no FDA-approved vaccine available for the prevention of human Q fever in the US, development of a safe and effective vaccine for the prevention of human Q fever remains an important goal for public health. However, there is a fundamental gap in knowledge regarding the mechanism of protective immunity against <i>C. burnetii</i> infection. To understand the mechanism of <i>C. burnetii</i> infection induced protective immunity, we examined if <i>C. burnetii</i> Nine Mile phase I (NMI) infection induces protection against <i>C. burnetii</i> reinfection in mice. Our results indicate that NMI-infected mice conferred significant protection against <i>C. burnetii</i> reinfection. We also found that NMI infection derived protection did not depend on the routes of infection and antibodies are required for NMI infection derived protection. In addition, NMI infection elicited a comparable level of protection in Wild type, CD4⁺ T cell deficient, and CD8⁺ T cell deficient mice, partial protection in B cell deficient mice but no protection in T cell deficient mice. These results suggest that both B cells and T cells are required for NMI-infection derived protection, but T cells may play a critical role. Therefore, the new generation vaccine for the prevention of human Q fever should be focused on boosting both humoral and T cell immune responses.