Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa
Xingyun Wang,
Cong Liu,
Nino Rcheulishvili,
Dimitri Papukashvili,
Fengfei Xie,
Jiao Zhao,
Xing Hu,
Kaiwei Yu,
Nuo Yang,
Xuehua Pan,
Xueyan Liu,
Peng George Wang,
Yunjiao He
Affiliations
Xingyun Wang
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Cong Liu
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Nino Rcheulishvili
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Dimitri Papukashvili
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Fengfei Xie
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Jiao Zhao
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Xing Hu
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Kaiwei Yu
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Nuo Yang
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Xuehua Pan
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Xueyan Liu
Department of Critical Medicine, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medicine College of Jinan University
Peng George Wang
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Yunjiao He
Department of Pharmacology, School of Medicine, Southern University of Science and Technology
Abstract Pseudomonas aeruginosa (PA) is a leading cause of hospital-acquired and ventilator-associated pneumonia. The multidrug-resistance (MDR) rate of PA is increasing making the management of PA a global challenge. Messenger RNA (mRNA) vaccines represent the most promising alternative to conventional vaccines and are widely studied for viral infection and cancer immunotherapy while rarely studied for bacterial infections. In this study, two mRNA vaccines encoding PcrV– the key component of the type III secretion system in Pseudomonas and the fusion protein OprF-I comprising outer membrane proteins OprF and OprI were constructed. The mice were immunized with either one of these mRNA vaccines or with the combination of both. Additionally, mice were vaccinated with PcrV, OprF, or the combination of these two proteins. Immunization with either mRNA-PcrV or mRNA-OprF-I elicited a Th1/Th2 mixed or slighted Th1-biased immune response, conferred broad protection, and reduced bacterial burden and inflammation in burn and systemic infection models. mRNA-PcrV induced significantly stronger antigen-specific humoral and cellular immune responses and higher survival rate compared with the OprF-I after challenging with all the PA strains tested. The combined mRNA vaccine demonstrated the best survival rate. Moreover, the mRNA vaccines showed the superiority over protein vaccines. These results suggest that mRNA-PcrV as well as the mixture of mRNA-PcrV and mRNA-OprF-I are promising vaccine candidates for the prevention of PA infection.