A Burkholderia pseudomallei Outer Membrane Vesicle Vaccine Provides Cross Protection against Inhalational Glanders in Mice and Non-Human Primates

Abstract

<i>Burkholderia mallei</i> is a Gram-negative, non-motile, facultative intracellular bacillus and the causative agent of glanders, a highly contagious zoonotic disease. <i>B. mallei</i> is naturally resistant to multiple antibiotics and there is concern for its potential use as a bioweapon, making the development of a vaccine against <i>B. mallei</i> of critical importance. We have previously demonstrated that immunization with multivalent outer membrane vesicles (OMV) derived from <i>B. pseudomallei</i> provide significant protection against pneumonic melioidosis. Given that many virulence determinants are highly conserved between the two species, we sought to determine if the <i>B. pseudomallei</i> OMV vaccine could cross-protect against <i>B. mallei</i>. We immunized C57Bl/6 mice and rhesus macaques with <i>B. pseudomallei</i> OMVs and subsequently challenged animals with aerosolized <i>B. mallei</i>. Immunization with <i>B. pseudomallei</i> OMVs significantly protected mice against <i>B. mallei</i> and the protection observed was comparable to that achieved with a live attenuated vaccine. OMV immunization induced the production of <i>B.mallei-</i>specific serum IgG and a mixed Th1/Th17 CD4 and CD8 T cell response in mice. Additionally, immunization of rhesus macaques with <i>B. pseudomallei</i> OMVs provided protection against glanders and induced <i>B.mallei</i>-specific serum IgG in non-human primates. These results demonstrate the ability of the multivalent OMV vaccine platform to elicit cross-protection against closely-related intracellular pathogens and to induce robust humoral and cellular immune responses against shared protective antigens.