Hcp1-loaded staphylococcal membrane vesicle vaccine protects against acute melioidosis

• Published in: Frontiers in immunology Vol. 13; p. 1089225
• Main Authors: Zhu, Keting, Li, Gang, Li, Jia, Zheng, Mingxia, Peng, Xiaohui, Rao, Yifan, Li, Ming, Zhou, Renjie, Rao, Xiancai
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.12.2022
• Subjects: Animals; Antibodies, Bacterial; Bacterial Vaccines; Burkholderia pseudomallei; Hcp1; Hemolysin Proteins; Immunology; Interleukin-6; melioidosis; Melioidosis - prevention & control; membrane vesicles; Mice; protection; Tumor Necrosis Factor-alpha; vaccine; vaccine; Burkholderia pseudomallei; melioidosis; protection; membrane vesicles; Hcp1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1089225

is the causal agent of melioidosis, a deadly tropical infectious disease that lacks a vaccine. On the basis of the attenuated RN4220-Δ (RN), we engineered the RN4220-Δ / strain (RN-Hcp1) to generate hemolysin-coregulated protein 1 (Hcp1)-loaded membrane vesicles ( MVs). The immunization of BALB/c mice with 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 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 MV-vaccinated mice relative to those that received the recombinant Hcp1 protein (rHcp1) or MVs derived from RN strain ( MVs). The MVs/adjuvant vaccine protected 70% of mice from lethal challenge. Immunization with MVs only protected 60% of mice, whereas vaccination with rHcp1 or MVs conferred no protection. Moreover, mice that received MVs/adjuvant and 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 MVs/adjuvant and MVs groups exhibited no culturable bacteria in their lungs, livers, and spleens five days postinfection. Overall, our data highlighted a new strategy for developing vaccine and showed that Hcp1-incorporated staphylococcal MV is a promising candidate for the prevention of acute melioidosis.