Synthetic Particulate Subunit Vaccines Co‐Delivering Multiple Antigens Induce Protective Immunity Against Melioidosis

Abstract

Melioidosis, caused by Burkholderia pseudomallei , is a life‐threatening disease and a potential biological warfare agent. Currently, no licensed vaccine is available for prevention. To address this unmet need, we bioengineered an endotoxin‐free Escherichia coli strain to assemble biopolymer inclusions coated with B. pseudomallei vaccine candidate antigens such as LolC, Omp85, OmpW, TssM, BopA, BimA, Hcp 1, Hcp 2, Hcp 3, and Hcp 6. These biopolymer particle (BP)‐based vaccines were formulated with the safe poly(I:C) adjuvant for intramuscular and intranasal administration in BALB/c mice. The vaccines were safe and induced specific and strong antibody responses. Additionally, the vaccines mediated secretion of Th1 and Th2 cytokines. No significant weight changes were observed in vaccinated groups compared with controls. In animal trials, immunized mice were challenged with a lethal dose of B. pseudomallei strain K96243 via the intraperitoneal route. Mice receiving BimA‐BP‐BopA and COM1 (a combination of BimA‐BP‐BopA, LolC‐BP‐Hcp1, and ME‐BM‐BP‐83 vaccine candidates) survived the challenge, with reduced bacterial burden in their livers and lungs when compared with empty BPs.