Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa

Wang，Xingyun1,2; Liu，Cong1; Rcheulishvili，Nino1; Papukashvili，Dimitri1; Xie，Fengfei1; Zhao，Jiao1; Hu，Xing1; Yu，Kaiwei1; Yang，Nuo1; Pan，Xuehua1; Liu，Xueyan2; Wang，Peng George1; He，Yunjiao1

2023-12-01

10.1038/s41541-023-00672-4

npj Vaccines   影响因子和分区

2059-0105

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.

SCI

英语

第一 ; 通讯

Science, Technology and Innovation Commission of Shenzhen Municipality[KQTD20200909113758004];

Immunology ; Research & Experimental Medicine

Immunology ; Medicine, Research & Experimental

WOS:000993502800002

NATURE PORTFOLIO

2-s2.0-85160268497

Scopus

1.Department of Pharmacology,School of Medicine,Southern University of Science and Technology,Shenzhen,China
2.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,Shenzhen,China

Wang，Xingyun,Liu，Cong,Rcheulishvili，Nino,et al. Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa[J]. npj Vaccines,2023,8(1).

Wang，Xingyun.,Liu，Cong.,Rcheulishvili，Nino.,Papukashvili，Dimitri.,Xie，Fengfei.,...&He，Yunjiao.(2023).Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa.npj Vaccines,8(1).

Wang，Xingyun,et al."Strong immune responses and protection of PcrV and OprF-I mRNA vaccine candidates against Pseudomonas aeruginosa".npj Vaccines 8.1(2023).