A thermostable messenger RNA based vaccine against rabies.
A thermostable messenger RNA based vaccine against rabies.
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DOI：
10.1371/journal.pntd.0006108
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发表时间：
2017-12
影响因子：
3.8
通讯作者：
Petsch B
中科院分区：
文献类型：
--
作者：
Stitz L;Vogel A;Schnee M;Voss D;Rauch S;Mutzke T;Ketterer T;Kramps T;Petsch B
虽然有效的狂犬病病毒疫苗已经存在了几十年，但每年狂犬病病毒感染仍然导致全球约50，000人死亡。这些病例大多发生在发展中国家，那里没有这些疫苗。其原因是细胞培养或卵生长狂犬病毒疫苗的成本过高，以及在狂犬病毒流行的许多地区缺乏功能性冷链。在这里，我们描述了一种编码狂犬病病毒糖蛋白（RABV-G）的基于非复制mRNA的狂犬病病毒疫苗的优异的耐温性。将疫苗从-80 ° C延长至+70 ° C储存数月不会影响mRNA疫苗的保护能力。通过诱导狂犬病特异性病毒中和抗体和保护小鼠免受致死性狂犬病感染证明了储存后的有效性。此外，将疫苗在+4° C至+56 ° C的振荡温度下储存20个循环以模拟疫苗运输期间冷链的中断，并不影响疫苗的免疫原性和保护特性，表明冷链的维持对于该疫苗不是必需的。传统的预防性疫苗需要在不间断的冷链中在受控温度下运输和储存。因此，许多疫苗的分发仅限于能够维持冷链的地区，这将许多国家的农村地区特别排除在持续的疫苗供应之外。不幸的是，一些可以通过接种疫苗预防的疾病，如狂犬病病毒感染，仍然在这些地区流行。因此，后勤方面的原因往往妨碍将拯救生命的疫苗运送到最需要的地区。在这里，我们描述了一种编码狂犬病病毒糖蛋白（RABV-G）的mRNA疫苗，该疫苗在高度可变的温度下储存后在小鼠攻击模型中保持保护性。这些结果表明，这种疫苗允许在冷链之外储存，因此可以到达世界上狂犬病病毒流行的所有地区。由于mRNA疫苗由相同的生物化学组分组成，无论编码的蛋白质如何，可以合理地假设狂犬病疫苗观察到的热稳定性是基于mRNA的疫苗的一般特征。
Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine’s immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine. Conventional prophylactic vaccines require transport and storage under controlled temperatures in an unbroken cold chain. Therefore, distribution of many vaccines is restricted to areas where the cold chain can be maintained which excludes especially rural areas in many countries from continues vaccine supply. Unfortunately, some diseases that can be prevented by vaccination, like the rabies virus infection, are still endemic in such areas. Therefore, logistic reasons often prevent delivery of life saving vaccines to areas in which they are most needed. Here, we describe an mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) that remains protective in a mouse challenge model upon storage at highly variable temperatures. These results suggest that such a vaccine allows storage outside the cold chain and can therefore reach all areas of the world where rabies virus is endemic. Since mRNA vaccines consist of the same biochemical components, irrespective of the encoded protein, it is reasonable to assume that the thermostability observed for the rabies vaccine is a general characteristic of mRNA based vaccines.
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影响因子：
2.7
作者：
Jones, Kathryn L.;Drane, Debbie;Gowans, Eric J.
通讯作者：
Gowans, Eric J.
影响因子：
5.5
作者：
Wirkas, Theo;Toikilik, Steven;Clements, C. John
通讯作者：
Clements, C. John
DOI：
10.4161/hv.5.1.6494
发表时间：
2009-01-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Chen, Dexiang;Tyagi, Anil;Braun, LaToya Jones
通讯作者：
Braun, LaToya Jones
DOI：
10.4161/hv.1.5.2110
发表时间：
2005-09-01
期刊：
HUMAN VACCINES
影响因子：
--
作者：
Sudarshan, M. K.;Mahendra, B. J.;Anandagiri, M. S.
通讯作者：
Anandagiri, M. S.
影响因子：
3.8
作者：
Schnee M;Vogel AB;Voss D;Petsch B;Baumhof P;Kramps T;Stitz L
通讯作者：
Stitz L