Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein
Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein
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DOI：
10.1016/j.vaccine.2024.03.008
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发表时间：
2024-04-04
期刊：
影响因子：
5.5
通讯作者：
Patel，Arvind H.
中科院分区：
文献类型：
--
作者：
Tandavanitj，Rapeepat;Setthapramote，Chayanee;Patel，Arvind H.
娄平病病毒（LIV）是一种蜱传的黄病毒，主要引起家畜疾病，特别是不列颠群岛的绵羊。以前批准用于兽医但现已停止使用的一种预防性疫苗是基于灭活的整个病毒粒子，可能通过诱导识别病毒包膜(E)蛋白的中和抗体提供保护。灭活疫苗的一个主要缺点是，按照病毒的第3类危险等级的规定，需要高度遏制传染性病毒传播的设施。本研究旨在开发高效的非感染性蛋白质候选疫苗。具体而言，由膜和包膜蛋白前体组成的可溶性包膜蛋白（sE）和病毒样颗粒（VLPs）在小鼠中产生、表征和研究了它们的免疫原性。结果表明，尽管两种抗原诱导的总抗包膜IgG含量相似，但VLPs诱导的病毒中和反应比sE更强。小鼠免疫血清中抗E蛋白单体抗体的缺失表明，VLPs诱导的中和抗体靶向的表位跨越了E蛋白多聚体的高度组织化结构，而sE诱导的抗体反应则集中在E蛋白单体上。因此，我们的研究结果表明，VLPs是一种很有前途的LIV疫苗候选物。
Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus. This study aimed to develop high-efficacy non-infectious protein-based vaccine candidates. Specifically, soluble envelope protein (sE), and virus-like particles (VLPs), comprised of the precursor of membrane and envelope proteins, were generated, characterized, and studied for their immunogenicity in mice. Results showed that the VLPs induced more potent virus neutralizing response compared to sE, even though the total anti-envelope IgG content induced by the two antigens was similar. Depletion of anti-monomeric E protein antibodies from mouse immune sera suggested that the neutralizing antibodies elicited by the VLPs targeted epitopes spanning the highly organized structure of multimer of the E protein, whereas the antibody response induced by sE focused on E monomers. Thus, our results indicate that VLPs represent a promising LIV vaccine candidate.