The Development of a Rabies Virus-Vectored Vaccine against Borrelia burgdorferi, Targeting BBI39.
The Development of a Rabies Virus-Vectored Vaccine against Borrelia burgdorferi, Targeting BBI39.
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DOI：
10.3390/vaccines12010078
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发表时间：
2024-01-12
期刊：
影响因子：
7.8
通讯作者：
Schnell MJ
中科院分区：
文献类型：
--
作者：
Rios S;Bhattachan B;Vavilikolanu K;Kitsou C;Pal U;Schnell MJ
莱姆病 (LD) 是美国、欧洲和亚洲最常见的蜱传疾病。伯氏疏螺旋体（Borrelia burgdorferi）是一种由蜱虫媒介肩胛硬蜱（Ixodes scapularis）传播的螺旋体细菌，在美国会引起LD。如果不及时治疗，可能会发生莱姆关节炎、心脏传导阻滞和脑膜炎。鉴于缺乏人类莱姆病疫苗，我们使用狂犬病病毒 (RABV) 疫苗载体 BNSP333 和外表面疏螺旋体蛋白 BBI39 开发了一种疫苗。 BBI39以前被用作重组蛋白疫苗，在攻击实验中具有保护作用；因此，我们决定在针对伯氏疏螺旋体的狂犬病病毒载体疫苗中利用这种保护性抗原。为了将 BBI39 整合到 RABV 病毒粒子中，我们通过分子克隆和逆转录遗传学病毒回收将 BBI39 与 RABV 糖蛋白的最终氨基酸融合，生成了嵌合 BBI39 抗原 BBI39RVG。在这里，我们通过免疫荧光和蛋白质印迹分析证明了 BBI39RVG 抗原已整合到 RABV 病毒体中。接种我们的 BPL 灭活 RABV-BBI39RVG (BNSP333-BBI39RVG) 疫苗的小鼠会诱导大量 BBI39 特异性抗体，并且这种抗体可以长期维持，最多可在疫苗接种后八个月。当通过注射器注射或受感染的蜱虫攻击伯氏疏螺旋体时，BBI39 抗体可以中和接种疫苗的小鼠体内的伯氏疏螺旋体，并减少受感染小鼠关节中关节炎的莱姆病病理学。总体而言，与重组蛋白疫苗相比，基于 RABV 的 LD 疫苗诱导了更多、更长期的抗体。与重组蛋白疫苗接种的小鼠相比，RABV 疫苗接种的小鼠体内的疏螺旋体 RNA 较低。本研究结果表明成功使用BBI39作为疫苗抗原和RABV作为LD疫苗载体。
Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine against Borrelia burgdorferi. To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39RVG, by fusing BBI39 with the final amino acids of the RABV glycoprotein by molecular cloning and viral recovery with reverse transcription genetics. Here, we have demonstrated that the BBI39RVG antigen was incorporated into the RABV virion via immunofluorescence and Western blot analysis. Mice vaccinated with our BPL inactivated RABV-BBI39RVG (BNSP333-BBI39RVG) vaccine induced high amounts of BBI39-specific antibodies, which were maintained long-term, up to eight months post-vaccination. The BBI39 antibodies neutralized Borrelia in vaccinated mice when challenged with Borrelia burgdorferi by either syringe injection or infected ticks and they reduced the Lyme disease pathology of arthritis in infected mouse joints. Overall, the RABV-based LD vaccine induced more and longer-term antibodies compared to the recombinant protein vaccine. This resulted in lower borrelial RNA in RABV-based vaccinated mice compared to recombinant protein vaccinated mice. The results of this study indicate the successful use of BBI39 as a vaccine antigen and RABV as a vaccine vector for LD.
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影响因子：
9.2
作者：
Dattwyler RJ;Gomes-Solecki M
通讯作者：
Gomes-Solecki M
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。
影响因子：
7.3
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
通讯作者：
Li, Xuguang
影响因子：
3.7
作者：
Adrion ER;Aucott J;Lemke KW;Weiner JP
通讯作者：
Weiner JP
影响因子：
3.1
作者：
Munson, EL;Du Chateau, BK;Schell, RF
通讯作者：
Schell, RF
影响因子：
11.8
作者：
Gomes-Solecki, Maria;Arnaboldi, Paul M.;Schutzer, Steven E.
通讯作者：
Schutzer, Steven E.