A novel inactivated whole-cell Pseudomonas aeruginosa vaccine that acts through the cGAS-STING pathway  

作　　者：Cuicui Ma Xiao Ma Boguang Jiang Hailong Pan Xueyuan Liao Li Zhang Wenfang Li Yingjie Luo Zhixue Shen Xingjun Cheng Mao Lian Zhenling Wang 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,and Collaborative Innovation Center of Biotherapy,Chengdu,610041,China [2]National Institutes for Food and Drug Control(NIFDC),Beijing,100050,China [3]Department of Quality Management,China National Biotec Group Company Limited,Beijing,100020,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第11期3256-3269,共14页信号转导与靶向治疗（英文）

基　　金：This study was supported by the Chinese Major Scientific and Technological Special Project for“Significant New Drugs Creation”,National Key Project(2019ZX09721-001-004-004);Key Technologies and Transformation Platform for Rapid Emergency Vaccine R&D for“the Sichuan Province Key R&D Program”(2020YFS0568).

摘　　要：Pseudomonas aeruginosa infection continues to be a major threat to global public health,and new safe and efficacious vaccines are needed for prevention of infections caused by P.aeruginosa.X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P.aeruginosa infection.However,the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation.Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P.aeruginosa by boosting T cells.The aim of the present study was to further explore the immunological mechanisms of the vaccine.Herein,P.aeruginosa PAO1,a widely used laboratory strain,was utilized to prepare the vaccine,and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1(XPa).By detecting CD86,CD80,and MHCII expression,we found that XPa fostered dentritic cell(DC)maturation by detecting.XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro,and DC finally underwent apoptosis and pyroptosis after XPa stimulation.In addition,DC stimulated by XPa induced CD8+T-cell proliferation in vitro and generated immunologic memory in vivo.Moreover,XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection.XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9.Chronic obstructive pulmonary disease(COPD)mice immunized with XPa could resist PAO1 infection.Therefore,a new mechanism of an X-ray-inactivated whole-cell vaccine against P.aeruginosa infection was discovered in this study.

关 键 词：VACCINE prevention utilized 

分 类 号：R186[医药卫生—流行病学]