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首页> 美国卫生研究院文献>other >Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1 hPIV-3 and RSV infections
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Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1 hPIV-3 and RSV infections

机译：表达hPIV-3 HN或F的仙台病毒重组疫苗引发保护性免疫并与第二种重组疫苗结合以预防hPIV-1hPIV-3和RSV感染

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The human parainfluenza viruses (hPIVs) and Respiratory Syncytial Virus (RSV) are the leading causes of serious respiratory illness in the human pediatric population. Despite decades of research, there are currently no licensed vaccines for either the hPIV or RSV pathogens. Here we describe the testing of hPIV-3 and RSV candidate vaccines using Sendai virus (SeV, murine PIV-1) as a vector. SeV was selected as the vaccine backbone, because it has been shown to elicit robust and durable immune activities in animal studies, and has already advanced to human safety trials as a xenogenic vaccine for hPIV-1. Two new SeV-based hPIV-3 vaccine candidates were first generated by inserting either the fusion (F) gene or hemagglutinin-neuraminidase (HN) gene from hPIV-3 into SeV. The resultant rSeV-hPIV3-F and rSeV-hPIV3-HN vaccines expressed their inserted hPIV-3 genes upon infection. The inoculation of either vaccine into cotton rats elicited binding and neutralizing antibody activities, as well as interferon-γ-producing T-cells. Vaccination of cotton rats resulted in protection against subsequent challenges with either homologous or heterologous hPIV-3. Furthermore, vaccination of cotton rats with a mixture of rSeV-hPIV3-HN and a previously described recombinant SeV expressing the F protein of RSV resulted in protection against three different challenge viruses: hPIV-3, hPIV-1 and RSV. Results encourage the continued development of the candidate recombinant SeV vaccines to combat serious respiratory infections of children.
机译：人类副流感病毒（hPIV）和呼吸道合胞病毒（RSV）是人类小儿严重呼吸道疾病的主要原因。尽管进行了数十年的研究，但目前尚无针对hPIV或RSV病原体的许可疫苗。在这里，我们描述了使用仙台病毒（SeV，鼠类PIV-1）作为载体测试hPIV-3和RSV候选疫苗的方法。 SeV之所以被选作疫苗的骨干，是因为它已被证明在动物研究中具有强大而持久的免疫活性，并且已作为hPIV-1的异种疫苗进入了人类安全性试验。通过将来自hPIV-3的融合（F）基因或血凝素神经氨酸酶（HN）基因插入SeV，首先生成了两种基于SeV的hPIV-3候选疫苗。所得的rSeV-hPIV3-F和rSeV-hPIV3-HN疫苗在感染后表达了其插入的hPIV-3基因。将两种疫苗接种到棉鼠中均引起结合和中和抗体活性，以及​​产生干扰素γ的T细胞。棉花大鼠的疫苗接种可防止其后受到同源或异源hPIV-3的攻击。此外，用rSeV-hPIV3-HN和先前描述的表达RSV F蛋白的重组SeV的混合物对棉花大鼠进行疫苗接种可预防三种不同的攻击病毒：hPIV-3，hPIV-1和RSV。结果鼓励继续开发候选重组SeV疫苗，以对抗儿童的严重呼吸道感染。

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