Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens
Construction and Immunogenicity of a Novel Multivalent Vaccine Prototype Based on Conserved Influenza Virus Antigens
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DOI：
10.3390/vaccines8020197
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发表时间：
2020-06-01
期刊：
影响因子：
7.8
通讯作者：
Kazaks, Andris
中科院分区：
文献类型：
--
作者：
Kirsteina, Anna;Akopjana, Inara;Kazaks, Andris
流感是一种急性、高度传染性呼吸道疾病，仍然对公众健康构成重大威胁。迫切需要更有效的疫苗接种策略，旨在诱导广泛的交叉保护，不仅针对季节性流感变种，而且还针对人畜共患和新出现的大流行流感毒株。许多引发这种交叉保护性免疫的保守蛋白靶点正在接受研究，其中研究最多的是来自血凝素柄的长α螺旋（LAH）和基质蛋白2离子通道（M2e）的胞外域。最近，我们报道了大肠杆菌表达的LAH（简称三茎蛋白）的三维结构和一些实际应用。在本研究中，我们研究了一组广泛保护性流感疫苗原型的免疫原性和功效，该原型基于整合到噬菌体 AP205 病毒样颗粒 (VLP) 中的流感三茎和三重 M2e (3M2e) 抗原。虽然单独含有 3M2e 的 VLP 可以诱导小鼠免受标准同源和异源病毒攻击的保护，但只有将两种保守流感抗原组合到单个 VLP 中才能完全保护小鼠免受高剂量同源 H1N1 流感感染。我们提出，将基因融合和化学偶联技术相结合，在单个颗粒上暴露两种不同的外来流感抗原，是产生广泛有效的候选疫苗的一种有前景的方法，可以预防不断出现的流感病毒株。
Influenza, an acute, highly contagious respiratory disease, remains a significant threat to public health. More effective vaccination strategies aimed at inducing broad cross-protection not only against seasonal influenza variants, but also zoonotic and emerging pandemic influenza strains are urgently needed. A number of conserved protein targets to elicit such cross-protective immunity have been under investigation, with long alpha-helix (LAH) from hemagglutinin stalk and ectodomain of matrix protein 2 ion channel (M2e) being the most studied ones. Recently, we have reported the three-dimensional structure and some practical applications of LAH expressed inEscherichia colisystem (referred to as tri-stalk protein). In the present study, we investigated the immunogenicity and efficacy of a panel of broadly protective influenza vaccine prototypes based on both influenza tri-stalk and triple M2e (3M2e) antigens integrated into phage AP205 virus-like particles (VLPs). While VLPs containing the 3M2e alone induced protection against standard homologous and heterologous virus challenge in mice, only the combination of both conserved influenza antigens into a single VLP fully protected mice from a high-dose homologous H1N1 influenza infection. We propose that a combination of genetic fusion and chemical coupling techniques to expose two different foreign influenza antigens on a single particle is a perspective approach for generation of a broadly-effective vaccine candidate that could protect against the constantly emerging influenza virus strains.