Evaluation of highly conserved Burkholderia pseudomallei outer membrane proteins as protective antigens against respiratory melioidosis

Burkholderia pseudomallei ( Bpm ), the etiological agent of melioidosis, lacks approved vaccines. However, several candidates have demonstrated protection in animal models. Interestingly, some of these vaccines can induce cross-protective immunity against the closely related species B. mallei . This led us to search the Bpm proteome for antigens that are highly conserved in more distantly related pathogenic Burkholderia species, which could potentially serve as components of a pan- Burkholderia vaccine. We identified three proteins, OmpA1, OmpA2, and Pal, which were coupled to an immunogenic gold nanoparticle (AuNP) platform. Intranasal immunization with these vaccines resulted in the induction of robust Th1/Th2-balanced responses and mucosal immunity, and the AuNP-OmpA1 and AuNP-OmpA2 vaccinated animals were significantly protected from a lethal Bpm respiratory challenge. Serum antibodies were highly cross-reactive to B. mallei and partially cross-reactive to B. multivorans and B. cenocepacia , indicating that the antigens contain highly conserved epitopes that can be incorporated in a pan- Burkholderia vaccine.