Division of Viral Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Sci Rep. 2018 Jan 12;8(1):561. doi: 10.1038/s41598-017-18973-9.
To improve the safety and efficacy of oral rotavirus vaccines, we developed an inactivated rotavirus vaccine (IRV) for parenteral administration. Since it remains unknown whether parenteral vaccination can induce mucosal immunity, we performed a comprehensive assessment of immune responses to IRV in mice with an adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on T and B cells in spleen and mLN of vaccinated mice. MN patch IRV vaccination induced a slight Th1 phenotype while IM vaccination induced a balanced Th1/Th2 phenotype. In addition, a dose-sparing effect was seen for rotavirus-specific serum IgG and neutralizing activity for both vaccination routes. Our study is the first to show that parenterally administered IRV can induce mucosal immunity in the gut, in addition to strong serum antibody response, and is a promising candidate vaccine in achieving global immunization against rotavirus.
为提高口服轮状病毒疫苗的安全性和有效性,我们开发了一种用于肠胃外给药的灭活轮状病毒疫苗(IRV)。由于尚不清楚肠胃外接种是否能诱导黏膜免疫,我们使用无佐剂的可溶解聚合物 MN 贴片或含铝佐剂的 IM 注射,对 IRV 在小鼠中的免疫反应进行了全面评估。我们证明,IRV 诱导接种小鼠脾脏和 mLN 中 T 和 B 细胞上肠道归巢受体 LPAM-1 的表达。MN 贴片 IRV 接种诱导轻微的 Th1 表型,而 IM 接种诱导平衡的 Th1/Th2 表型。此外,两种接种途径的轮状病毒特异性血清 IgG 和中和活性都观察到了剂量节省效应。我们的研究首次表明,肠胃外给予的 IRV 除了能诱导强烈的血清抗体反应外,还能诱导肠道黏膜免疫,是实现全球轮状病毒免疫接种的有前途的候选疫苗。