DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model

Frontiers in Immunology

Immunology

Sathya N. Thulasi Raman¹  Jun Gao¹  Jianguo Wu¹  Marsha S. Russell¹  Caroline Gravel¹  Simon Sauve¹  Annabelle Pfeifle²  Wanyue Zhang²  Levi A. Tamming²  Xuguang Li²  Michael Rosu-Myles²  Emmanuel Laryea²  Michael J. W. Johnston³  Lisheng Wang⁴  Wangxue Chen⁵  Diana Duque⁵  Anh Tran⁵  Jingxin Cao⁶  David Safronetz⁶  Reem M. Alsulaiman⁷  Rowa Y. Alhabbab⁸  Anwar M. Hashem⁹ 

[1] Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada;Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada;Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada;Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada and World Health Organization Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada;Department of Chemistry, Carleton University, Ottawa, ON, Canada;Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada;Human Health Therapeutics Research Center, National Research Council of Canada, Ottawa, ON, Canada;National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada;Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia;Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia;Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;

关键词: SARS-CoV-2;    coronavirus;    vaccination;    DNA;    antibody response;    pathology;   

DOI  :  10.3389/fimmu.2021.785349

 received in 2021-09-29, accepted in 2021-12-10,  发布年份 2022

来源: Frontiers

【 摘 要 】

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

【 授权许可】

Unknown   
Copyright © 2022 Tamming, Duque, Tran, Zhang, Pfeifle, Laryea, Wu, Raman, Gravel, Russell, Hashem, Alsulaiman, Alhabbab, Gao, Safronetz, Cao, Wang, Chen, Johnston, Sauve, Rosu-Myles and Li