Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates.
Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates.
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组合F-G免疫原作为NIPAH和呼吸道合胞病毒疫苗候选。
DOI：
10.3390/v13101942
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发表时间：
2021-09-28
期刊：
影响因子：
--
通讯作者：
Watterson D
中科院分区：
文献类型：
--
作者：
Isaacs A;Cheung STM;Thakur N;Jaberolansar N;Young A;Modhiran N;Bailey D;Graham SP;Young PR;Chappell KJ;Watterson D
尼帕病毒（NiV）和呼吸道合胞病毒（RSV）具有两种参与细胞粘附和膜融合的表面糖蛋白，这两种蛋白都是疫苗的潜在靶点。大多数疫苗开发集中在NiV的附着（G）蛋白，其是免疫显性靶标。相反，RSV的融合（F）蛋白是疫苗开发中的主要靶标。尽管如此，在NiV F和RSV G中已经描述了中和表位，使它们成为疫苗设计的替代靶标。通过合理的设计，我们已经开发了适用于遗传学上不同的NiV和RSV的疫苗策略，其包含F和G蛋白（FxG）。在小鼠免疫模型中，我们发现NiV FxG引起能够中和假型NiV和能够逃避两种已知F特异性抗体中和的NiV突变体的改善的免疫应答。RSV FxG引发针对F和G两者的免疫应答，并且能够中和RSV;然而，这劣于单独的F的免疫应答。尽管如此，RSV FxG还是引发了针对G内已知保护性表位的反应，该表位在RSV A和B亚组中是保守的，这可能在体内提供额外的保护。我们的结论是，包括F和G抗原在一个单一的设计提供了一个精简的亚单位疫苗策略，对新兴和建立的病原体，具有更广泛的保护对NiV的潜力。
Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.
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