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Published on: June 8, 2012
An outer membrane vesicle vaccine prevents lung pathology in a macaque model of pneumonic melioidosis
Sarah M Baker1,2, Erik W Settles3, Kimberly R Celona3
1Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA, USA. smbaker@uw.edu.
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.
Insights
An outer membrane vesicle (OMV) vaccine shows promise for preventing melioidosis, a serious bacterial infection. This novel vaccine candidate has demonstrated efficacy in non-human primates, paving the way for human trials.
Area of Science:
- Microbiology
- Vaccinology
- Infectious Diseases
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is an emerging infectious disease with high mortality.
- The pathogen exhibits intrinsic antibiotic resistance, necessitating alternative interventions like vaccines.
- Current vaccine development for melioidosis has not progressed beyond pre-clinical rodent models.
Purpose of the Study:
- To evaluate the efficacy of an outer membrane vesicle (OMV) vaccine against melioidosis.
- To assess the immunogenicity of the OMV vaccine in non-human primates.
- To determine the potential for advancing the OMV vaccine to human clinical trials.
Main Methods:
- An outer membrane vesicle (OMV) vaccine was administered to non-human primates (NHP).
- Vaccine efficacy was assessed using survivability, biotelemetry, and clinical pathology.
- Serologic assays were employed to measure IgG and IgA responses to OMV antigens.
- Macrophage opsonophagocytosis assays were performed using NHP immune sera.
Main Results:
- The OMV vaccine successfully prevented pulmonary melioidosis in non-human primates.
- Vaccination induced systemic and mucosal IgG and IgA responses to OMV surface proteins and polysaccharides.
- NHP immune sera enhanced opsonophagocytosis of B. pseudomallei by macrophages.
- Human sera showed responses to key OMV antigens correlated with melioidosis survival.
Conclusions:
- The OMV vaccine is a promising candidate for preventing melioidosis.
- The vaccine elicits robust immune responses in non-human primates.
- These findings support the advancement of the OMV vaccine to human phase 1 clinical trials.
