H5N1 Vaccine-Specific B Cell Responses in Ferrets Primed with Live Attenuated Seasonal Influenza Vaccines
H5N1 Vaccine-Specific B Cell Responses in Ferrets Primed with Live Attenuated Seasonal Influenza Vaccines
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DOI：
10.1371/journal.pone.0004436
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发表时间：
2009-02-11
期刊：
影响因子：
3.7
通讯作者：
Jin, Hong
中科院分区：
文献类型：
--
作者：
Cheng, Xing;Eisenbraun, Michael;Jin, Hong
背景：已经在从未暴露于甲型流感病毒感染的小鼠和雪貂中生产并评估了H5N1减毒流感活疫苗（Suguitan等人，Plos Medicine, e360: 1541, 2006）。然而，对H5N1减毒活疫苗诱导的免疫反应先前存在的流感异亚型免疫尚未得到评价。方法和主要发现：采用敏感抗原特异性B细胞ELISpot法检测原代和召回B细胞对H5N1减毒活疫苗病毒的反应，以研究预先存在的异亚型流感免疫对雪貂H5N1特异性B细胞免疫反应的影响。H5N1减毒活疫苗病毒A/Hong Kong/213/03和A/Vietnam/1203/04在鼻内接种后诱导可测量的h5特异性IgM和IgG分泌B细胞。然而，在先前接种过三价流感减毒活疫苗（H1N1、H3N2和B）的雪貂中，在接种H5N1后检测到h5特异性IgG分泌细胞的时间明显提前，频率也更高。启动研究进一步揭示了B细胞对H5反应更快的原因是B细胞对血凝素H1蛋白的交叉反应性免疫。此外，接种H1N1疫苗病毒能够诱导保护性反应，将H5N1疫苗病毒的复制限制在与先前接种H5N1疫苗病毒相当的水平，而不影响H5N1疫苗病毒诱导的抗体反应。结论：研究结果表明，以往接种季节性流感疫苗可能会加速H5N1 ca疫苗的免疫反应，而异亚型免疫可能有利于大流行的防范。
Background: Live attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360: 1541, 2006). However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.Methodology and Principal Findings: Primary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B) vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response.Conclusion: The findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness.