Human PIV-2 recombinant Sendai virus (rSeV) elicits durable immunity and combines with two additional rSeVs to protect against hPIV-1, hPIV-2, hPIV-3, and RSV
Human PIV-2 recombinant Sendai virus (rSeV) elicits durable immunity and combines with two additional rSeVs to protect against hPIV-1, hPIV-2, hPIV-3, and RSV
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DOI：
10.1016/j.vaccine.2009.01.041
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发表时间：
2009-03-13
期刊：
影响因子：
5.5
通讯作者：
Hurwitz, Julia L.
中科院分区：
文献类型：
--
作者：
Jones, Bart;Zhan, Xiaoyan;Hurwitz, Julia L.
人类副流感病毒（hPIV）和呼吸道合胞病毒（RSV）是婴幼儿呼吸道病毒性疾病导致住院的主要原因，但目前尚无疫苗可用。在这里，我们描述了在棉鼠模型中使用重组仙台病毒（rSeV）作为这些呼吸道病毒的候选疫苗载体。通过将 hPIV-2 的融合 (F) 基因或血凝素-神经氨酸酶 (HN) 基因插入 rSeV 基因组中，生成了两种新的基于仙台病毒 (SeV) 的 hPIV-2 疫苗构建体。将任一疫苗接种到棉鼠体内都会引发针对同源和异源 hPIV-2 病毒分离株的中和抗体。疫苗引发针对 hPIV-2 的强大且持久的抗体，并且用单独或混合疫苗免疫的棉鼠完全免受下呼吸道 hPIV-2 感染。单次接种 rSeV 疫苗的免疫反应是持久的，并且棉鼠在接种疫苗后长达 11 个月内可以免受病毒攻击。一次接种表达 hPIV-2-HN 的构建体和两种额外的 rSeV（表达 RSV 的 F 蛋白和 hPIV-3 的 HN 蛋白）的混合物，可产生针对攻击病毒 hPIV-1、hPIV-2、hPIV-3 和 RSV 的保护作用。结果表明，SeV 载体是四种不同副粘病毒的有希望的候选疫苗，每种副粘病毒都会导致儿童严重呼吸道感染。 (C) 2009 Elsevier Ltd. 保留所有权利。
The human parainfluenza viruses (hPIVs) and respiratory syncytial viruses (RSVs) are the leading causes of hospitalizations due to respiratory viral disease in infants and young children, but no vaccines are yet available. Here we describe the use of recombinant Sendai viruses (rSeVs) as candidate vaccine vectors for these respiratory viruses in a cotton rat model. Two new Sendai virus (SeV)-based hPIV-2 vaccine constructs were generated by inserting the fusion (F) gene or the hemagglutinin-neuraminidase (HN) gene from hPIV-2 into the rSeV genome. The inoculation of either vaccine into cotton rats elicited neutralizing antibodies toward both homologous and heterologous hPIV-2 virus isolates, The vaccines elicited robust and durable antibodies toward hPIV-2, and cotton rats immunized with individual or mixed vaccines were fully protected against hPIV-2 infections of the lower respiratory tract. The immune responses toward a single inoculation with rSeV vaccines were long-lasting and cotton rats were protected against viral challenge for as long as 11 months after vaccination. One inoculation with a mixture of the hPIV-2-HN-expressing construct and two additional rSeVs (expressing the F protein of RSV and the HN protein of hPIV-3) resulted in protection against challenge viruses hPIV-1, hPIV-2, hPIV-3, and RSV. Results identify SeV vectors as promising vaccine candidates for four different paramyxoviruses, each responsible for serious respiratory infections in children. (C) 2009 Elsevier Ltd. All rights reserved.