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

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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Publication Details

Journal
Nature Communications
Published
2025-12-09
DOI
https://doi.org/10.1038/s41467-025-67213-6
Primary Topic
Burkholderia infections and melioidosis
Type
article
Field-Weighted Citation Impact
0.00
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article

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

C Dao, Philip L. Felgner, Derek A. Pociask, Kalen Hall et al.
Nature Communications
Burkholderia infections and melioidosis
article

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

C Dao, Philip L. Felgner, Derek A. Pociask, Kalen Hall, Kimberly R. Celona, Anthony E. Gregory, Mark Mayo, Christine M. Davitt, Erik W. Settles, Austin B. Shannon, Kasi Russell‐Lodrigue, Celeste Woerle, Paul Keim, Heesik Yoon, Sarah M. Baker, William C. Wimley, Lisa A. Morici, Bart J. Currie, Chad J. Roy, Janice M. Moser, James B. McLachlan, Rafael Ramiro de Assis, Aarti Jain
article en

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.

Nature CommunicationsVol. 17(1)
Tulane University (US), University of Washington (US), Northern Arizona University (US), University of California, Irvine (US), Charles Darwin University (AU), Sanofi (France) (FR), Menzies School of Health Research (AU)
Openalex Percentile: Top 49%
Burkholderia infections and melioidosis
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