Comparison of Immune Responses to Different Versions of VLP Associated Stabilized RSV Pre-Fusion F Protein
Comparison of Immune Responses to Different Versions of VLP Associated Stabilized RSV Pre-Fusion F Protein
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DOI：
10.3390/vaccines7010021
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发表时间：
2019-02-15
期刊：
影响因子：
7.8
通讯作者：
Morrison, Trudy G.
中科院分区：
文献类型：
--
作者：
Cullen, Lori M.;Schmidt, Madelyn R.;Morrison, Trudy G.
开发呼吸道合胞病毒（RSV）疫苗的努力主要集中在RSV融合蛋白上。该蛋白的融合前构象诱导最有效的中和抗体，并且是疫苗开发中最近努力的焦点。在RSV F蛋白（DS-Cav 1突变蛋白）中首次鉴定出稳定融合前构象的突变后，已描述了其他突变稳定的融合前F蛋白。为了确定稳定的融合前F蛋白的替代版本是否存在差异，我们探索了含有五种不同融合前F蛋白（包括DS-Cav 1蛋白）的病毒样颗粒（VLP）作为疫苗候选物的用途。这五种前F蛋白的表达、它们组装成VLP、它们在VLP中的融合前构象稳定性、它们与抗F单克隆抗体的反应性以及它们在小鼠免疫后诱导免疫应答的特征在于，将含有DS-Cavl前F蛋白的VLP与含有四种替代的融合前F蛋白的VLP进行比较。测量由使用两种不同的可溶性融合前F蛋白作为靶标阻断原型单克隆抗体结合的每种VLP诱导的抗F IgG的浓度。我们的结果表明，替代VLP相关的稳定化融合前RSV F蛋白的构象和免疫原性均不同于DS-Cav 1 VLP的构象和免疫原性。
Efforts to develop a vaccine for respiratory syncytial virus (RSV) have primarily focused on the RSV fusion protein. The pre-fusion conformation of this protein induces the most potent neutralizing antibodies and is the focus of recent efforts in vaccine development. Following the first identification of mutations in the RSV F protein (DS-Cav1 mutant protein) that stabilized the pre-fusion conformation, other mutant stabilized pre-fusion F proteins have been described. To determine if there are differences in alternate versions of stabilized pre-fusion F proteins, we explored the use, as vaccine candidates, of virus-like particles (VLPs) containing five different pre-fusion F proteins, including the DS-Cav1 protein. The expression of these five pre-F proteins, their assembly into VLPs, their pre-fusion conformation stability in VLPs, their reactivity with anti-F monoclonal antibodies, and their induction of immune responses after the immunization of mice, were characterized, comparing VLPs containing the DS-Cav1 pre-F protein with VLPs containing four alternative pre-fusion F proteins. The concentrations of anti-F IgG induced by each VLP that blocked the binding of prototype monoclonal antibodies using two different soluble pre-fusion F proteins as targets were measured. Our results indicate that both the conformation and immunogenicity of alternative VLP associated stabilized pre-fusion RSV F proteins are different from those of DS-Cav1 VLPs.