Intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity.
Intranasal immunization with a replication-deficient adenovirus vector expressing glycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity.
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DOI：
10.1016/j.vaccine.2004.07.041
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发表时间：
2005-01
期刊：
影响因子：
5.5
通讯作者：
J. Shanley;Carol A. Wu
中科院分区：
文献类型：
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作者：
J. Shanley;Carol A. Wu
通过将受人 CMV IE-1 启动子控制的 MCMV gH 完整开放阅读框插入复制缺陷型腺病毒 5 的 E-1 区，构建了疫苗载体，命名为 AdV-gH。用 AdV-gH 体外感染 QB1-293 细胞和小鼠胚胎细胞，IFA 检测到 MCMV gH 的表达。通过鼻内途径给予 AdV-gH (1 × 107PFU) 免疫 BALB/c 小鼠可诱导体液反应，在 100% 疫苗的血清中检测到抗体。支气管肺泡灌洗液、粪便悬浮液和阴道冲洗液中也检测到了 MCMV gH 抗体。 MCMV（1×105PFU）鼻内攻击后10天，免疫小鼠肺和唾液腺的病毒滴度与对照组相比显着降低，但并未阻止病毒感染。初次免疫后 30 天，将小鼠再次暴露于 AdV-gH 会诱导血清抗体反应显着增强。当再次鼻内注射 MCMV 时，这些小鼠的肺和唾液腺中的 MCMV 滴度进一步降低。这种策略对于减少 CMV 感染跨粘膜表面的水平传播和改变宿主对 CMV 的免疫力可能很重要。
A vaccine vector, designated AdV-gH, was constructed by inserting the complete open reading frame of MCMV gH under control of the human CMV IE-1 promoter into the E-1 region of a replication-deficient adenovirus 5. In vitro infection of QB1-293 cells and mouse embryo cells with AdV-gH resulted in expression of MCMV gH detected by IFA. Immunization of BALB/c mice with AdV-gH (1 × 107PFU) given by the intranasal route induced a humoral response with antibody detected in serum of 100% of vaccines. Antibody to MCMV gH was also detected in the bronchoalveolar lavage, fecal suspensions and vaginal washings. The viral titer of lung and salivary gland of immunized mice 10 days after intranasal challenge with MCMV (1 × 105PFU) were significantly reduced compared to controls, but virus infection was not prevented. Re-exposure of mice to AdV-gH 30 days after primary immunization induced a significant boost of serum antibody response. When rechallenged with MCMV intranasally, these mice had further reduction of MCMV titers in the lung and salivary glands. Such a strategy may be important in reducing horizontal transmission of CMV infections across mucosal surfaces and in altering host immunity to CMV.