Preclinical evaluation of a recombinant MVA expressing the hemagglutinin-neuraminidase envelope protein of parainfluenza virus 5 (Mammalian orthorubulavirus 5)

D.S.O. Daian e Silva , T.M.G. Pinho , R.P. Rocha , S.B. Oliveira , G.M. Franco , E.F. Barbosa-Stancioli , F.G. Da Fonseca
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Abstract

PIV 5 (Mammalian orthorubulavirus 5 - ICTV, 2021, previously known as Parainfluenza virus 5) is one of the main causes of ITB (infectious tracheobronchitis) affecting dogs, with a global distribution and potential to generate outbreaks from time to time. The currently available vaccines against the disease do not prevent the symptoms, require a high number of doses, and use adjuvants that, in addition to the cost of production, are responsible for adverse reactions, sometimes severe. Such drawbacks have raised the interest for new vaccine's development against ITB. In this context, we designed a recombinant immunogen based on the modified Vaccinia virus Ankara (MVA) expressing the hemagglutinin-neuraminidase (HN) envelope protein of PIV 5, and evaluated the immunogenic potential of this vaccine in C57BL/6 female mice. For the immunogenicity analyzes, epitopes of CD8+ T cell for the MHC-I murine alleles were predicted in silico, evaluated in vitro through flow cytometry and ELISA assays, and were used to evaluate the CD8+ T cell responses. The efficient expression of the envelope protein by the recombinant vector, allied to the immunogenic responses in vivo, highlights the potential of our recombinant MVA as a vaccine against PIV 5.

表达副流感病毒5的血凝素-神经氨酸酶包膜蛋白的重组MVA的临床前评价
PIV 5(哺乳动物原发性呼吸道病毒5-ICTV,2021,以前称为副流感病毒5)是影响狗的传染性气管支气管炎的主要原因之一,在全球范围内分布,并有可能不时引发疫情。目前可用的针对该疾病的疫苗不能预防症状,需要大量剂量,并且使用的佐剂除了生产成本外,还会导致不良反应,有时甚至是严重的不良反应。这些缺点引起了人们对针对ITB开发新疫苗的兴趣。在此背景下,我们设计了一种基于修饰的安卡拉痘苗病毒(MVA)的重组免疫原,表达PIV 5的血凝素-神经氨酸酶(HN)包膜蛋白,并评估了该疫苗在C57BL/6雌性小鼠中的免疫原性潜力。对于免疫原性分析,在计算机中预测MHC-I小鼠等位基因的CD8+T细胞表位,通过流式细胞术和ELISA测定在体外进行评估,并用于评估CD8+T淋巴细胞反应。重组载体对包膜蛋白的有效表达,与体内免疫原性反应相结合,突出了我们的重组MVA作为PIV 5疫苗的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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