AUTHOR=Zhu Keting , Li Gang , Li Jia , Zheng Mingxia , Peng Xiaohui , Rao Yifan , Li Ming , Zhou Renjie , Rao Xiancai 

TITLE=Hcp1-loaded staphylococcal membrane vesicle vaccine protects against acute melioidosis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1089225

DOI=10.3389/fimmu.2022.1089225

ISSN=1664-3224

ABSTRACT=<p><italic>Burkholderia pseudomallei</italic> is the causal agent of melioidosis, a deadly tropical infectious disease that lacks a vaccine. On the basis of the attenuated <italic>Staphylococcus aureus</italic> RN4220-Δ<italic>agr</italic> (RN), we engineered the RN4220-Δ<italic>agr</italic>/<italic>pdhB-hcp1</italic> strain (RN-Hcp1) to generate <italic>B. pseudomallei</italic> hemolysin-coregulated protein 1 (Hcp1)-loaded membrane vesicles (<sup>hcp1</sup>MVs). The immunization of BALB/c mice with <sup>hcp1</sup>MVs mixed with adjuvant by a three-dose regimen increased the serum specific IgG production. The serum levels of inflammatory factors, including TNF-α and IL-6, in <sup>hcp1</sup>MV-vaccinated mice were comparable with those in PBS-challenged mice. The partial adjuvant effect of staphylococcal MVs was observed with the elevation of specific antibody titer in <sup>hcp1</sup>MV-vaccinated mice relative to those that received the recombinant Hcp1 protein (rHcp1) or MVs derived from RN strain (<sup>Δagr</sup>MVs). The <sup>hcp1</sup>MVs/adjuvant vaccine protected 70% of mice from lethal <italic>B. pseudomallei</italic> challenge. Immunization with <sup>hcp1</sup>MVs only protected 60% of mice, whereas vaccination with rHcp1 or <sup>Δagr</sup>MVs conferred no protection. Moreover, mice that received <sup>hcp1</sup>MVs/adjuvant and <sup>hcp1</sup>MVs immunization had low serum TNF-α and IL-6 levels and no inflammatory infiltration in comparison with other groups. In addition, all surviving mice in <sup>hcp1</sup>MVs/adjuvant and <sup>hcp1</sup>MVs groups exhibited no culturable bacteria in their lungs, livers, and spleens five days postinfection. Overall, our data highlighted a new strategy for developing <italic>B. pseudomallei</italic> vaccine and showed that Hcp1-incorporated staphylococcal MV is a promising candidate for the prevention of acute melioidosis.</p>