Zhan Xiaoyan, Slobod Karen S, Krishnamurthy Sateesh, Luque Laura E, Takimoto Toru, Jones Bart, Surman Sherri, Russell Charles J, Portner Allen, Hurwitz Julia L
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
Vaccine. 2008 Jun 25;26(27-28):3480-8. doi: 10.1016/j.vaccine.2008.04.022. Epub 2008 May 1.
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-gamma-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.
人副流感病毒(hPIVs)和呼吸道合胞病毒(RSV)是导致人类儿童严重呼吸道疾病的主要病因。尽管经过了数十年的研究,但目前针对hPIV或RSV病原体均无获批的疫苗。在此,我们描述了使用仙台病毒(SeV,鼠类PIV-1)作为载体对hPIV-3和RSV候选疫苗进行的测试。选择SeV作为疫苗骨架,是因为在动物研究中已证明其能引发强大且持久的免疫活性,并且作为hPIV-1的异种疫苗已进入人体安全性试验阶段。首先通过将hPIV-3的融合(F)基因或血凝素神经氨酸酶(HN)基因插入SeV,构建了两种基于SeV的新型hPIV-3候选疫苗。所得的rSeV-hPIV3-F和rSeV-hPIV3-HN疫苗在感染时表达其插入的hPIV-3基因。将任何一种疫苗接种到棉鼠体内均可引发结合和中和抗体活性以及产生γ干扰素的T细胞。对棉鼠进行疫苗接种可使其免受同源或异源hPIV-3的后续攻击。此外,用rSeV-hPIV3-HN与先前描述的表达RSV F蛋白的重组SeV混合物对棉鼠进行疫苗接种,可使其免受三种不同攻击病毒的侵害:hPIV-3、hPIV-1和RSV。这些结果鼓励继续研发候选重组SeV疫苗以对抗儿童严重的呼吸道感染。