Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Mol Pharm. 2012 Jan 1;9(1):156-67. doi: 10.1021/mp200392g. Epub 2011 Dec 15.
Sublingual (SL) delivery, a noninvasive immunization method that bypasses the intestinal tract for direct entry into the circulation, was evaluated with an adenovirus (Ad5)-based vaccine for Ebola. Mice and guinea pigs were immunized via the intramuscular (IM), nasal (IN), oral (PO) and SL routes. SL immunization elicited strong transgene expression in and attracted CD11c(+) antigen presenting cells to the mucosa. A SL dose of 1 × 10⁸ infectious particles induced Ebola Zaire glycoprotein (ZGP)-specific IFN-γ⁺ T cells in spleen, bronchoalveolar lavage, mesenteric lymph nodes and submandibular lymph nodes (SMLN) of naive mice in a manner similar to the same dose given IN. Ex vivo CFSE and in vivo cytotoxic T lymphocyte (CTL) assays confirmed that SL immunization elicits a notable population of effector memory CD8+ T cells and strong CTL responses in spleen and SMLN. SL immunization induced significant ZGP-specific Th1 and Th2 type responses unaffected by pre-existing immunity (PEI) that protected mice and guinea pigs from lethal challenge. SL delivery protected more mice with PEI to Ad5 than IM injection. SL immunization also reduced systemic anti-Ad5 T and B cell responses in naive mice and those with PEI, suggesting that secondary immunizations could be highly effective for both populations.
舌下（SL）给药是一种非侵入性免疫接种方法，可绕过肠道直接进入循环系统，已用于埃博拉的基于腺病毒（Ad5）的疫苗评估。通过肌肉内（IM）、鼻内（IN）、口服（PO）和 SL 途径对小鼠和豚鼠进行免疫接种。SL 免疫接种在粘膜中引起强烈的转基因表达，并吸引 CD11c（+）抗原呈递细胞。以 1×10⁸个感染颗粒的 SL 剂量，以与 IN 相同剂量相似的方式，在无反应性小鼠的脾脏、支气管肺泡灌洗液、肠系膜淋巴结和颌下淋巴结（SMLN）中诱导出埃博拉扎伊尔糖蛋白（ZGP）特异性 IFN-γ⁺T 细胞。体外 CFSE 和体内细胞毒性 T 淋巴细胞（CTL）测定证实，SL 免疫接种可在脾脏和 SMLN 中产生显著的效应记忆 CD8+T 细胞和强大的 CTL 反应。SL 免疫接种诱导了显著的 ZGP 特异性 Th1 和 Th2 型反应，不受预先存在的免疫（PEI）的影响，可保护小鼠和豚鼠免受致命挑战。与 IM 注射相比，SL 给药可保护更多具有 PEI 的小鼠免受 Ad5 的侵害。SL 免疫接种还降低了无反应性和具有 PEI 的小鼠中的全身性抗 Ad5 T 和 B 细胞反应，表明二次免疫接种对这两种人群都可能非常有效。
