An outer membrane vesicle vaccine prevents lung pathology in a macaque model of pneumonic melioidosis

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Abstract
Melioidosis is an emerging infectious disease caused by the intracellular bacterial pathogen, Burkholderia pseudomallei. Infection of humans and animals can occur through multiple routes of bacterial entry resulting in life-threatening pneumonia and/or bacteremia. B. pseudomallei is inherently resistant to multiple antibiotics and mortality rates are high despite therapeutic intervention. Development of an effective vaccine could protect at-risk individuals, such as those who reside in highly endemic areas, military personnel, diabetics, and travelers. Despite decades of pursuit, no candidate vaccine for melioidosis has advanced beyond pre-clinical testing in rodent models. Here, we demonstrate that an outer membrane vesicle (OMV) vaccine prevents pulmonary disease in non human primates (NHP) using survivability, biotelemetry, and clinical pathology assessments. Using two independent serologic assays, we demonstrate that vaccination in rhesus macaques is associated with systemic and mucosal IgG and IgA to OMV surface proteins and polysaccharides. We also show that NHP immune sera promotes opsonophagocytosis by macrophages and that human sera responses to several key OMV antigens are associated with survival in melioidosis. Collectively, these results attest to the potential efficacy of the OMV vaccine and lay the groundwork for its advancement to human phase 1 clinical trials.

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