Humoral response induced after intranasal vaccination with heat inactivated Acinetobacter baumannii protects immunodeficient mice against hypervirulent LAC-4 strain

Background Acinetobacter baumannii is an opportunistic bacterium that causes serious nosocomial infections, including pneumonia and bacteremia, especially in immunocompromised individuals. Methods Here, we first evaluated the protective efficacy of a vaccination protocol with the heat-killed (HK) A. baumannii strain LAC-4 in various models of immunodeficient C57BL/6 mice challenged with pulmonary infection by LAC-4. We then examined the ability of HK LAC-4 to stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors in vitro . Results We observed that mice deficient in Th1 (IL-12p35 -/- , IFN-γ -/- ), Th17 (IL-17RA -/- ) and T cells (δTCR -/- , TAP1 -/- , CD3 -/- ) display higher susceptibility to LAC-4 infection, but that our protocol improves their resistance. In contrast, vaccinated B cell-deficient (MuMT -/- ) mice appear unable to control the infection, demonstrating that humoral immunity is essential to vaccine protection. Vaccination of wild-type mice with an HK Δ itrA strain deficient for capsule production failed to induce protection, showing that protective antibodies are mainly directed against the capsule. Our vaccination protocol also confers increased protection in wild-type mice vaccinated and then treated with cyclophosphamide; an immunosuppressive drug described to strongly increase the susceptibility of mice to A. baumannii infection. Finally, we demonstrate that HK LAC-4 can induce the activation of human monocyte-derived dendritic cells and T lymphocytes from PBMCs of healthy donors, suggesting that it may activate the human adaptive immune system and induce a protective memory response against A. baumannii . Conclusions Overall, our results demonstrate that administration of HK bacteria can induce protective immunity against A. baumannii in both immuno-competent and immuno-compromised mice and that these HK bacteria can activate the human adaptive immune system.