DNA lipid nanoparticle vaccine targeting outer surface protein C affords protection against homologous Borrelia burgdorferi needle challenge in mice

Frontiers in Immunology

Immunology

Sathya N. Thulasi Raman¹  Grant Frahm¹  Jianguo Wu¹  Caroline Gravel¹  Casey Lansdell¹  Devina Patel¹  Simon Sauve¹  Jun Gao²  Annabelle Pfeifle³  Levi Tamming³  Wanyue Zhang³  Xuguang Li³  Michael Rosu-Myles³  Michael J. W. Johnston⁴  George Chaconas⁵  Lisheng Wang⁶  Emmanuel Laryea⁶  Jonathon Cecillon⁷  Wangxue Chen⁸ 

[1] Centre for Oncology, Radiopharmaceuticals and Research, 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 Oncology, Radiopharmaceuticals and Research, 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 Vaccines, Clinical Trials and Biostatistics, 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 Oncology, Radiopharmaceuticals and Research, 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 Oncology, Radiopharmaceuticals and Research, 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 and Molecular Biology and Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada;Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada;Department of Chemistry and Biomolecular Sciences, Faculty of Science, University of Ottawa, Ottawa, ON, Canada;Human Health Therapeutics Research Center, National Research Council of Canada, Ottawa, ON, Canada;

关键词: Lyme disease;    lipid nanoparticle;    outer surface protein C;    antibodies;    carditis;    lymphadenopathy;    DNA vaccine;    Lyme borreliosis;   

DOI  :  10.3389/fimmu.2023.1020134

 received in 2022-08-15, accepted in 2023-03-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe incidence of Lyme disease (LD) in Canada and the United States has risen over the last decade, nearing 480,000 cases each year. Borrelia burgdorferi sensu lato, the causative agent of LD, is transmitted to humans through the bite of an infected tick, resulting in flu-like symptoms and often a characteristic bull’s-eye rash. In more severe cases, disseminated bacterial infection can cause arthritis, carditis and neurological impairments. Currently, no vaccine is available for the prevention of LD in humans.MethodsIn this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of B. burgdorferi.ResultsVaccination of C3H/HeN mice with two doses of the candidate vaccine induced significant OspC-type A-specific antibody titres and borreliacidal activity. Analysis of the bacterial burden following needle challenge with B. burgdorferi (OspC-type A) revealed that the candidate vaccine afforded effective protection against homologous infection across a range of susceptible tissues. Notably, vaccinated mice were protected against carditis and lymphadenopathy associated with Lyme borreliosis.DiscussionOverall, the results of this study provide support for the use of a DNA-LNP platform for the development of LD vaccines.

【 授权许可】

Unknown   
Copyright © 2023 Pfeifle, Thulasi Raman, Lansdell, Zhang, Tamming, Cecillon, Laryea, Patel, Wu, Gravel, Frahm, Gao, Chen, Chaconas, Sauve, Rosu-Myles, Wang, Johnston and Li