Protective immunity by an engineered DNA vaccine for Mayaro virus
Protective immunity by an engineered DNA vaccine for Mayaro virus
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DOI：
10.1371/journal.pntd.0007042
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发表时间：
2019-02-01
影响因子：
3.8
通讯作者：
Muthumani, Kar
中科院分区：
文献类型：
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作者：
Choi, Hyeree;Kudchodkar, Sagar B.;Muthumani, Kar
马亚罗病毒（MAYV）是一种由蚊子传播的新发传染病，可引起急性发热性疾病、皮疹、头痛和恶心，在某些患者中可能会转变为失能性、持续性关节痛。自从1954年在特立尼达岛发现MAYV以来，MAYV感染病例主要局限于那里和南美洲的北方国家，但最近，在加勒比海的一些岛屿国家报告了MAYV病例。伴随这些报告的是新的媒介，包括伊蚊。最近与寨卡病毒和基孔肯雅病毒的全球传播有关的蚊子能够传播MAYV，如果这是真的，可能会促进MAYV的传播超出其目前的范围。尽管它的地位作为一种新兴的病毒，有没有许可的疫苗，以防止MAYV感染，也没有治疗it.here，我们描述了一种新的DNA疫苗，scMAYV-E，编码一个合成设计的共识MAYV包膜序列的开发和测试。用该疫苗对小鼠进行体内电穿孔增强免疫诱导了有效的体液应答，包括中和抗体以及对MAYV包膜中多个表位的强烈T细胞应答。重要的是，这些scMAYV-E诱导的免疫反应保护易感小鼠免受MAYV攻击后的发病率和死亡率。作者摘要马亚罗病毒（MAYV）是一种蚊子传播的病毒，可引起发烧，头痛，寒战，恶心和关节疼痛，感染后可持续数月。由于蚊子传播增加，病例数量增加，以及流行病的威胁强调了它作为一种新兴病毒的重要性，但没有获得许可的疫苗来预防Mayaro感染，也没有治疗方法。在这项研究中，我们收集了免疫系统如何对MAYV感染做出反应的基本知识，我们评估了一种新型合成DNA包膜疫苗（scMAYV-E）在小鼠中的有效性。对小鼠免疫应答的分析表明，该疫苗诱导了有效的T细胞免疫和抗体。接受疫苗然后用活的MAYV攻击的小鼠被保护免受Mayaro病。这些数据提供了证据表明，基于DNA的MAYV疫苗可能能够预防马亚罗病。因此，scMAYV-E疫苗是MAYV疫苗开发的有希望的一步。未来的测试将评估这种疫苗是否是阻止MAYV传播和保护个人免受Mayaro病的可行方法。
Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.Author summary Mayaro virus (MAYV) is a mosquito-transmitted virus that causes fever, headache, chills, nausea and joint pain that can last for months after infection. The rising number of cases, due to increased mosquito circulation, and the threat of an epidemic emphasize its importance as an emerging virus, but there are no licensed vaccines to prevent Mayaro infection nor therapeutics to treat it. In this study, we gathered fundamental knowledge on how the immune system responds to MAYV infection, and we evaluated the efficacy of a novel, synthetic DNA envelope vaccine (scMAYV-E) in mice. Analysis of immune responses in mice demonstrated that this vaccine induces potent T cell immunity and antibodies. Mice who receive the vaccine and then are challenged with live MAYV are protected against Mayaro disease. This data provides evidence that the DNA-based MAYV vaccine may be able to prevent Mayaro disease. Thus, the scMAYV-E vaccine is a promising step forward for MAYV vaccine development. Future testing will evaluate whether this vaccine is a viable means to halt the spread of MAYV and protect individuals from Mayaro disease.