Drug Design, Development and Therapy (Dec 2023)
Immunoinformatics Prediction and Protective Efficacy of Vaccine Candidate PiuA-PlyD4 Against Streptococcus Pneumoniae
Abstract
Chenglin Miao,1,* Yali Cui,1– 3,* Yingying Li,1 Qianqian Qi,1 Wenling Shang,1 Huilian Chen,2,3 Yujie Gao,2,3 Ruomei Yuan,2,3 Qichen Long,4 Wenjing Wu,1 Xia Wang,1 Ziyi Yan,1 Yongmei Jiang1,5 1Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Laboratory Medicine, Meishan Women and Children’s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, Meishan, Sichuan Province, People’s Republic of China; 3Department of Laboratory Medicine, West China Second University Hospital (Tianfu), Sichuan University/Sichuan Provincial Children’s Hospital, Meishan, Sichuan Province, People’s Republic of China; 4Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyi Yan; Yongmei Jiang, Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28 8857050 ; +86 28 85501543, Email [email protected]; [email protected]: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments.Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored.Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81± 2.32) × 105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process.Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.Keywords: Streptococcus pneumoniae, fusion protein vaccine, PiuA-PlyD4, immunoinformatics prediction, protective efficacy
