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

被引：17

作者：

Pfeifle, Annabelle ^{[1
,2
,3
]}

Raman, Sathya Thulasi N. ^{[1
,2
]}

Lansdell, Casey ^{[1
,2
]}

Zhang, Wanyue ^{[1
,2
,3
]}

Tamming, Levi ^{[1
,2
,3
]}

Cecillon, Jonathon ^{[4
]}

Laryea, Emmanuel ^{[3
]}

Patel, Devina ^{[1
,2
]}

Wu, Jianguo ^{[1
,2
]}

Gravel, Caroline ^{[1
,2
]}

Frahm, Grant ^{[1
,2
]}

Gao, Jun ^{[1
,2
,5
]}

Chen, Wangxue ^{[6
]}

Chaconas, George ^{[7
,8
]}

Sauve, Simon ^{[1
,2
]}

Rosu-Myles, Michael ^{[1
,2
,3
]}

Wang, Lisheng ^{[3
]}

Johnston, Michael J. W. ^{[1
,2
,9
]}

Li, Xuguang ^{[1
,2
,3
]}

机构：

[1] Hlth Canada, Ctr Oncol Radiopharmaceut & Res, Hlth Prod & Food Branch, Biol & Radiopharmaceut Drugs Directorate, Ottawa, ON, Canada

[2] World Hlth Org, Collaborating Ctr Standardizat & Evaluat Biol, Ottawa, ON, Canada

[3] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada

[4] Univ Ottawa, Fac Sci, Dept Chem & Biomol Sci, Ottawa, ON, Canada

[5] Hlth Canada, Ctr Vaccines Clin Trials & Biostat, Hlth Prod & Food Branch, Biol & Radiopharmaceut Drugs Directorate, Ottawa, ON, Canada

[6] Natl Res Council Canada, Human Hlth Therapeut Res Ctr, Ottawa, ON, Canada

[7] Univ Calgary, Snyder Inst Chron Dis, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB, Canada

[8] Univ Calgary, Snyder Inst Chron Dis, Cumming Sch Med, Dept Microbiol Innunol & Infect Dis, Calgary, AB, Canada

[9] Carleton Univ, Dept Chem, Ottawa, ON, Canada

来源：

FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷

基金：

加拿大健康研究院;

关键词：

Lyme disease; lipid nanoparticle; outer surface protein C; antibodies; carditis; lymphadenopathy; DNA vaccine; Lyme borreliosis; LYME-DISEASE; IMMUNE-RESPONSE; OSPC; INFECTION; DELIVERY; SIZE; MANIFESTATIONS; IMMUNIZATION; SPIROCHETE; EXPRESSION;

D O I：

10.3389/fimmu.2023.1020134

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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.

引用

页数：11

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