AUTHOR=Feng Junxia , Deng Yingying , Fu Mengjiao , Hu Xueyuan , Luo Wenbo , Lu Zhiyu , Dai Lupeng , Yang Huiying , Zhao Xiaodong , Du Zongmin , Wen Bohai , Jiang Lingxiao , Zhou Dongsheng , Jiao Jun , Xiong Xiaolu 

TITLE=Construction of a Live-Attenuated Vaccine Strain of Yersinia pestis EV76-B-SHUΔpla and Evaluation of Its Protection Efficacy in a Mouse Model by Aerosolized Intratracheal Inoculation

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00473

DOI=10.3389/fcimb.2020.00473

ISSN=2235-2988

ABSTRACT=<p>Plague, which is caused by <italic>Yersinia pestis</italic>, is one of the most dangerous infectious diseases. No FDA-approved vaccine against plague is available for human use at present. To improve the immune safety of <italic>Y. pestis</italic> EV76 based live attenuated vaccine and to explore the feasibility of aerosolized intratracheal inoculation (i.t.) route for vaccine delivery, a plasminogen activator protease (<italic>pla</italic>) gene deletion mutant of the attenuated <italic>Y. pestis</italic> strain EV76-B-SHU was constructed, and its residual virulence and protective efficacy were evaluated in a mouse model via aerosolized intratracheal inoculation (i.t.) or via subcutaneous injection (s.c.). The residual virulence of EV76-B-SHUΔ<italic>pla</italic> was significantly reduced compared to that of the parental strain EV76-B-SHU following i.t. and s.c. infection. The EV76-B-SHUΔ<italic>pla</italic> induced higher levels of mucosal antibody sIgA in the bronchoalveolar lavage fluid of mice immunized by i.t. but not by s.c.. Moreover, after lethal challenge with <italic>Y. pestis</italic> biovar Microtus strain 201 (avirulent in humans), the protective efficacy and bacterial clearance ability of the EV76-B-SHUΔ<italic>pla</italic>-i.t. group were comparable to those of the EV76-B-SHUΔ<italic>pla</italic>-s.c. and EV76-B-SHU immunized groups. Thus, the EV76-B-SHUΔ<italic>pla</italic> represents an excellent live-attenuated vaccine candidate against pneumonic plague and aerosolized i.t. represents a promising immunization route in mouse model.</p>