The Contribution of Systemic and Pulmonary Immune Effectors to Vaccine-Induced Protection from H5N1 Influenza Virus Infection
The Contribution of Systemic and Pulmonary Immune Effectors to Vaccine-Induced Protection from H5N1 Influenza Virus Infection
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DOI：
10.1128/jvi.07205-11
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Subbarao, Kanta
中科院分区：
文献类型：
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作者：
Lau, Yuk-Fai;Wright, Amber R.;Subbarao, Kanta
减毒流感活疫苗（LAIVs）在动物模型中对流感攻击提供保护和在人类中预防疾病方面是有效的。我们之前的研究表明，laiv会引发一系列免疫效应物，并且成功诱导小鼠的肺细胞和体液免疫需要疫苗病毒的肺复制。在小鼠中建立了上呼吸道免疫（URTI）模型以模拟人类情况，其中疫苗病毒不会在下呼吸道复制，使我们能够在没有显著肺免疫的情况下评估H5N1 LAIV对高致病性H5N1病毒攻击的保护作用。我们的研究结果表明，在一次剂量的H5N1 LAIV后，肺部流感特异性淋巴细胞是清除肺部攻击病毒的主要贡献者，而血清和脾CD8(+) T细胞中流感特异性酶联免疫吸附试验（ELISA）抗体的贡献可以忽略不计。在两剂H5N1 LAIV后，实现了对H5N1攻击的完全保护，并与抗体反应的成熟有关。虽然从接受两剂疫苗的小鼠身上被动转移血清可以防止攻击后幼稚受体的死亡，但小鼠表现出明显的体重减轻，具有高H5N1病毒肺滴度。这些数据强调了粘膜免疫在介导对H5N1感染的最佳保护中的重要性。了解在呼吸道中有效诱导和建立这些保护性免疫效应的要求，为未来更合理、更有效的疫苗方法铺平了道路。
Live attenuated influenza vaccines (LAIVs) are effective in providing protection against influenza challenge in animal models and in preventing disease in humans. We previously showed that LAIVs elicit a range of immune effectors and that successful induction of pulmonary cellular and humoral immunity in mice requires pulmonary replication of the vaccine virus. An upper respiratory tract immunization (URTI) model was developed in mice to mimic the human situation, in which the vaccine virus does not replicate in the lower respiratory tract, allowing us to assess the protective efficacy of an H5N1 LAIV against highly pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity. Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza-specific lymphocytes are the main contributors to clearance of challenge virus from the lungs and that contributions of influenza-specific enzyme-linked immunosorbent assay (ELISA) antibodies in serum and splenic CD8(+) T cells were negligible. Complete protection from H5N1 challenge was achieved after two doses of H5N1 LAIV and was associated with maturation of the antibody response. Although passive transfer of sera from mice that received two doses of vaccine prevented lethality in naive recipients following challenge, the mice showed significant weight loss, with high pulmonary titers of the H5N1 virus. These data highlight the importance of mucosal immunity in mediating optimal protection against H5N1 infection. Understanding the requirements for effective induction and establishment of these protective immune effectors in the respiratory tract paves the way for a more rational and effective vaccine approach in the future.