Effect of a Novel Trivalent Vaccine Formulation against Acute Lung Injury Caused by Pseudomonas aeruginosa.

Abstract

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294), the outer membrane domain (#190-342) of OprF (OprF#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ)). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.