Bidokhti Mehdi R M, Ullman Karin, Hammer Anne Sofie, Jensen Trine Hammer, Chriél Mariann, Byrareddy Siddappa N, Baule Claudia
Department of Virology, Immunobiology and Parasitology, The National Veterinary Institute (SVA), SE-751 89 Uppsala, Sweden.
Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center (UNMC), Omaha, NE 68198-5800, USA.
Vaccines (Basel). 2019 Aug 2;7(3):79. doi: 10.3390/vaccines7030079.
A full understanding of the immune response to astrovirus (AstV) infection is required to treat and control AstV-induced gastroenteritis. Relative contributions of each arm of the immune system in restricting AstV infection remain unknown. In this study, two novel subunit AstV vaccines derived from capsid protein (CP) of mink AstV (MAstV) such as CPΔN (spanning amino acids 161-775) and CPΔC (spanning amino acids 1-621) were evaluated. Their immunogenicity and cytokine production in mice, as well as protective efficacy in mink litters via maternal immunization, were studied. Truncated CPs induced higher levels of serum anti-CP antibodies than CP, with the highest level for CPΔN. No seronegativity was detected after booster immunization with either AstV CP truncates in both mice and mink. All mink moms stayed seropositive during the entire 104-day study. Furthermore, lymphoproliferation responses and Th1/Th2 cytokine induction of mice splenocytes ex vivo re-stimulated by truncated CPs were significantly higher than those by CP, with the highest level for CPΔN. Immunization of mink moms with truncated CPs could suppress virus shedding and clinical signs in their litters during a 51-day study after challenge with a heterogeneous MAstV strain. Collectively, AstV truncated CPs exhibit better parameters for protection than full-length CP.
为了治疗和控制星状病毒(AstV)引起的肠胃炎,需要全面了解对AstV感染的免疫反应。免疫系统各部分在限制AstV感染中的相对作用尚不清楚。在本研究中,评估了两种源自水貂AstV(MAstV)衣壳蛋白(CP)的新型亚单位AstV疫苗,如CPΔN(跨度为氨基酸161 - 775)和CPΔC(跨度为氨基酸1 - 621)。研究了它们在小鼠中的免疫原性和细胞因子产生,以及通过母体免疫在水貂幼崽中的保护效果。截短的CPs诱导产生的血清抗CP抗体水平高于CP,其中CPΔN的水平最高。在用AstV CP截短物对小鼠和水貂进行加强免疫后,未检测到血清阴性。在整个104天的研究中,所有水貂妈妈均保持血清阳性。此外,截短的CPs体外再刺激小鼠脾细胞后的淋巴细胞增殖反应和Th1/Th2细胞因子诱导水平显著高于CP,其中CPΔN的水平最高。在用异源MAstV毒株攻击后的51天研究中,用水貂妈妈接种截短的CPs可以抑制其幼崽中的病毒脱落和临床症状。总体而言,AstV截短的CPs比全长CP表现出更好的保护参数。