Induction of heterosubtypic immunity to influenza virus by intranasal immunization
Induction of heterosubtypic immunity to influenza virus by intranasal immunization
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DOI：
10.1128/jvi.01615-07
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发表时间：
2008-02-01
影响因子：
5.4
通讯作者：
Kang, Sang-Moo
中科院分区：
文献类型：
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作者：
Quan, Fu-Shi;Compans, Richard W.;Kang, Sang-Moo
已知从活流感病毒感染中恢复可诱导异亚型免疫。相反，灭活疫苗诱导的免疫主要是亚型特异性的。在这项研究中，我们研究了灭活流感病毒诱导的异亚型保护性免疫。用灭活的流感病毒A/PR 8（H1N1）鼻内免疫小鼠提供了针对同源病毒和相同亚型A/WSN（H1N1）内的漂移病毒的完全保护，但不针对异亚型病毒A/菲律宾（H3 N2）。然而，灭活病毒与霍乱毒素作为佐剂共同给药，即使在CD 4（+）或CD 8（+）T细胞耗竭的条件下，也能提供完全的异亚型保护，而没有观察到疾病。免疫相关性的分析前的挑战和postchallenge表明，体液免疫反应，在肺和血清中的交叉中和活性发挥了重要作用，赋予保护性免疫对异亚型的挑战。这项研究对开发针对新出现的致病性流感病毒的广泛交叉反应疫苗具有重要意义。
Recovery from live influenza virus infection is known to induce heterosubtypic immunity. In contrast, immunity induced by inactivated vaccines is predominantly subtype specific. In this study, we investigated the heterosubtypic protective immunity induced by inactivated influenza virus. Intranasal immunization of mice with inactivated influenza virus A/PR8 (H1N1) provided complete protection against the homologous virus and a drift virus within the same subtype, A/WSN (H1N1), but not against the heterosubtypic virus A/Philippines (H3N2). However, coadministration of inactivated virus with cholera toxin as an adjuvant conferred complete heterosubtypic protection, without observed illness, even under conditions of CD4(+) or CD8(+) T-cell depletion. Analysis of immune correlates prior to challenge and postchallenge indicated that humoral immune responses with cross-neutralizing activity in lungs and in sera play a major role in conferring protective immunity against heterosubtypic challenge. This study has significant implications for developing broadly cross-reactive vaccines against newly emerging pathogenic influenza viruses.