DNA lipid nanoparticle vaccine targeting outer surface protein C affords protection against homologous Borrelia burgdorferi needle challenge in mice.
DNA lipid nanoparticle vaccine targeting outer surface protein C affords protection against homologous Borrelia burgdorferi needle challenge in mice.
复制标题
靶向外表面蛋白 C 的 DNA 脂质纳米颗粒疫苗可为小鼠提供针对同源伯氏疏螺旋体针刺攻击的保护。
DOI：
10.3389/fimmu.2023.1020134
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发表时间：
2023
影响因子：
7.3
通讯作者：
Li, Xuguang
中科院分区：
文献类型：
--
作者：
Pfeifle, Annabelle;Raman, Sathya Thulasi N.;Lansdell, Casey;Zhang, Wanyue;Tamming, Levi;Cecillon, Jonathon;Laryea, Emmanuel;Patel, Devina;Wu, Jianguo;Gravel, Caroline;Frahm, Grant;Gao, Jun;Chen, Wangxue;Chaconas, George;Sauve, Simon;Rosu-Myles, Michael;Wang, Lisheng;Johnston, Michael J. W.;Li, Xuguang
关键词：
过去十年，加拿大和美国莱姆病 (LD) 的发病率不断上升，每年接近 48 万例。伯氏疏螺旋体（Borrelia burgdorferi sensu lato）是 LD 的病原体，通过受感染的蜱虫叮咬传播给人类，导致类似流感的症状，并且通常会出现典型的牛眼皮疹。在更严重的情况下，播散性细菌感染可导致关节炎、心脏炎和神经损伤。目前，尚无疫苗可用于预防人类 LD。在这项研究中，我们开发了一种脂质纳米颗粒 (LNP) 封装的 DNA 疫苗，编码伯氏疏螺旋体外表面蛋白 C A 型 (OspC-A 型)。 用两剂候选疫苗接种 C3H/HeN 小鼠可诱导显着的 OspC A 型特异性抗体滴度和疏螺旋体酸活性。对伯氏疏螺旋体（OspC-A 型）针刺后的细菌负荷分析表明，候选疫苗可有效保护一系列易感组织免受同源感染。值得注意的是，接种疫苗的小鼠可以预防与莱姆疏螺旋体病相关的心脏炎和淋巴结病。总体而言，本研究结果为利用DNA-LNP平台开发LD疫苗提供了支持。
The 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. In this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of B. burgdorferi. Vaccination 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. Overall, 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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影响因子：
9.2
作者：
Dattwyler RJ;Gomes-Solecki M
通讯作者：
Gomes-Solecki M
影响因子：
7.8
作者：
Francis JE;Skakic I;Dekiwadia C;Shukla R;Taki AC;Walduck A;Smooker PM
通讯作者：
Smooker PM
影响因子：
2.7
作者：
Grunwald T;Ulbert S
通讯作者：
Ulbert S
影响因子：
4.8
作者：
Guibinga GH;Sahay B;Brown H;Cooch N;Chen J;Yan J;Reed C;Mishra M;Yung B;Pugh H;Schultheis K;Esquivel RN;Weiner DB;Humeau LH;Broderick KE;Smith TRF
通讯作者：
Smith TRF
影响因子：
3.1
作者：
Crother, TR;Champion, CI;Lovett, MA
通讯作者：
Lovett, MA