Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection
Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection
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DOI：
10.1016/j.vaccine.2010.03.032
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发表时间：
2010-05-14
期刊：
影响因子：
5.5
通讯作者：
Chang, Jun
中科院分区：
文献类型：
--
作者：
Kim, Sol;Jang, Ji-Eun;Chang, Jun
呼吸道合胞病毒（RSV）是婴儿和幼儿严重下呼吸道疾病的主要原因。尽管其作为病原体的重要性，但没有针对RSV的许可疫苗。RSV的融合蛋白（F）是保护性抗病毒免疫应答的潜在重要靶标。在这里，我们研究了重组复制缺陷型腺病毒（rAd）为基础的疫苗表达的F蛋白（氨基酸155-524）的可溶性F1片段在小鼠模型中引起的免疫应答。通过密码子优化，rAd分泌型F1片段的表达量显著增加。强的粘膜伊加应答由密码子优化的疫苗rAd/F1 co的单次鼻内免疫诱导，而不是由rAd/F1 wt诱导。用rAd/F1 co单次鼻内免疫提供了对随后的RSV攻击的有效保护。有趣的是，在rAd/F1 co免疫小鼠中既没有检测到针对F蛋白的血清IG也没有检测到针对F蛋白的T细胞应答，这表明rAd/F1 co的保护性免疫主要通过粘膜伊加诱导介导。事实上，霍乱毒素B亚单位的共同交付显着增强粘膜！优化疫苗的伊加应答，这与保护效力相关。综上所述，我们的数据表明，rAd/F1 co单次鼻内给药足以提供保护，代表了一种有前途的针对RSV感染的预防性疫苗接种方案。(C)2010爱思唯尔有限公司保留所有权利。
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The fusion (F) protein of RSV is a potentially important target for protective antiviral immune responses. Here, we studied the immune responses elicited by recombinant replication-deficient adenovirus (rAd)-based vaccines expressing the soluble F1 fragment of F protein (amino acids 155-524) in murine model. The expression of secreted F1 fragment by rAd was significantly increased by codon optimization. Strong mucosal IgA response was induced by single intranasal immunization of codon-optimized vaccine, rAd/F1co, but not by rAd/F1 wt. A single intranasal immunization with rAd/F1co provided potent protection against subsequent RSV challenge. Interestingly, neither serum Ig nor T-cell response directed to F protein was detected in the rAd/F1co-immune mice, suggesting that protective immunity by rAd/F1co is mainly mediated through mucosal IgA induction. Indeed, co-delivery of cholera toxin B subunit significantly enhanced mucosa! IgA responses by the optimized vaccine, which correlates with protective efficacy. Taken together, our data demonstrate that a single intranasal administration of rAd/F1co is sufficient for the protection and represents a promising prophylactic vaccination regimen against RSV infection. (C) 2010 Elsevier Ltd. All rights reserved.