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
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.
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页数:11
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共 59 条
[1]  
[Anonymous], 2022, Climate Change Indicators: Atmospheric Concentrations of Greenhouse Gases
[2]   CARDITIS IN LYME-DISEASE SUSCEPTIBLE AND RESISTANT STRAINS OF LABORATORY MICE INFECTED WITH BORRELIA-BURGDORFERI [J].
ARMSTRONG, AL ;
BARTHOLD, SW ;
PERSING, DH ;
BECK, DS .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1992, 47 (02) :249-258
[3]   Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns [J].
Bachmann, Martin F. ;
Jennings, Gary T. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (11) :787-796
[4]   Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J].
Baden, Lindsey R. ;
El Sahly, Hana M. ;
Essink, Brandon ;
Kotloff, Karen ;
Frey, Sharon ;
Novak, Rick ;
Diemert, David ;
Spector, Stephen A. ;
Rouphael, Nadine ;
Creech, C. Buddy ;
McGettigan, John ;
Khetan, Shishir ;
Segall, Nathan ;
Solis, Joel ;
Brosz, Adam ;
Fierro, Carlos ;
Schwartz, Howard ;
Neuzil, Kathleen ;
Corey, Larry ;
Gilbert, Peter ;
Janes, Holly ;
Follmann, Dean ;
Marovich, Mary ;
Mascola, John ;
Polakowski, Laura ;
Ledgerwood, Julie ;
Graham, Barney S. ;
Bennett, Hamilton ;
Pajon, Rolando ;
Knightly, Conor ;
Leav, Brett ;
Deng, Weiping ;
Zhou, Honghong ;
Han, Shu ;
Ivarsson, Melanie ;
Miller, Jacqueline ;
Zaks, Tal .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (05) :403-416
[5]   Infection history of the blood-meal host dictates pathogenic potential of the Lyme disease spirochete within the feeding tick vector [J].
Bhatia, Bharti ;
Hillman, Chad ;
Carracoi, Valentina ;
Cheff, Britney N. ;
Tilly, Kit ;
Rosa, Patricia A. .
PLOS PATHOGENS, 2018, 14 (04)
[6]   Clinical spectrum of Lyme disease [J].
Cardenas-de la Garza, Jesus Alberto ;
De la Cruz-Valadez, Estephania ;
Ocampo-Candiani, Jorge ;
Welsh, Oliverio .
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, 2019, 38 (02) :201-208
[7]   The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes [J].
Comstedt, Par ;
Schuler, Wolfgang ;
Meinke, Andreas ;
Lundberg, Urban .
PLOS ONE, 2017, 12 (09)
[8]   Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin [J].
Crother, TR ;
Champion, CI ;
Whitelegge, JP ;
Aguilera, R ;
Wu, XY ;
Blanco, DR ;
Miller, JN ;
Lovett, MA .
INFECTION AND IMMUNITY, 2004, 72 (09) :5063-5072
[9]   The year that shaped the outcome of the OspA vaccine for human Lyme disease [J].
Dattwyler, Raymond J. ;
Gomes-Solecki, Maria .
NPJ VACCINES, 2022, 7 (01)
[10]   Microemulsion extrusion technique: a new method to produce lipid nanoparticles [J].
de Jesus, Marcelo Bispo ;
Radaic, Allan ;
Zuhorn, Inge S. ;
de Paula, Eneida .
JOURNAL OF NANOPARTICLE RESEARCH, 2013, 15 (10)