Soler Eric, Parez Nathalie, Passet Bruno, Dubuquoy Catherine, Riffault Sabine, Pillot Matthieu, Houdebine Louis-Marie, Schwartz-Cornil Isabelle
Biologie du Développement et de la Reproduction, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
Vaccine. 2007 Aug 21;25(34):6373-80. doi: 10.1016/j.vaccine.2007.06.011. Epub 2007 Jun 27.
Development of a safe, cheap and efficient vaccine against rotavirus is important to reduce the morbidity and mortality associated with gastroenteritis in infants worldwide. High quantities of two inner core rotavirus-derived proteins (VP2 and a nonglycosylated mutant VP6 (VP6(NG)) from the RF81 bovine strain) were produced in the milk of transgenic rabbits. We show here that rectal administration of partially purified milk-derived VP2 and VP6(NG) proteins with the detoxified LT(R192G) adjuvant almost completely prevented fecal shedding induced by a highly infectious challenge in mice with the murine ECw strain. The vaccine generated rotavirus-specific fecal secretory IgA, systemic IgG and IgA and a rotavirus-specific Th1 response. We thus demonstrate in clinically feasible settings that mass production of viral protein in transgenic milk is a promising way to generate subunit vaccine against rotavirus.
开发一种安全、廉价且高效的轮状病毒疫苗对于降低全球婴儿肠胃炎相关的发病率和死亡率至关重要。在转基因兔的乳汁中大量产生了两种源自轮状病毒内核心的蛋白（VP2和来自RF81牛株的非糖基化突变体VP6（VP6(NG)））。我们在此表明，将部分纯化的源自乳汁的VP2和VP6(NG)蛋白与解毒的LT(R192G)佐剂经直肠给药，几乎完全预防了小鼠经鼠ECw株高感染性攻击后诱导的粪便排毒。该疫苗产生了轮状病毒特异性粪便分泌型IgA、全身性IgG和IgA以及轮状病毒特异性Th1反应。因此，我们在临床可行的环境中证明，在转基因乳汁中大规模生产病毒蛋白是生产轮状病毒亚单位疫苗的一种有前景的方法。
