V Murugaiah, S J Watson, R F Cunliffe, N J Temperton, S T Reece, P Kellam, J S Tregoning
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引用次数: 0
摘要
开发通用流感疫苗可能需要了解以前接触流感病毒的情况(通过接种疫苗或感染),以及这种情况如何形成接种疫苗后的抗体库,有时也称为 "原始抗原罪 "或 "抗原印记"。虽然动物模型可以有更明确的接触史,但它们缺乏人类 B 细胞群。具有完整人类免疫球蛋白基因座的转基因小鼠可用于研究受控感染史导致的类人抗体进化。在这里,我们评估了 Intelliselect 转基因小鼠(Kymouse)对流感的反应。我们的研究表明,Kymouse 感染 H1N1、H3N2 或 B/Yam 流感病毒后易发病,并能诱导出对所有三种流感病毒株的强结合和中和抗体反应。这项研究表明,人类 B 细胞谱系小鼠可用于流感病毒研究,为进一步研究抗体反应提供了工具。
A transgenic mouse with a humanised B cell repertoire mounts an antibody response to influenza infection and vaccination
The development of a universal influenza vaccine likely requires an understanding of previous exposure to influenza virus (through vaccination or infection) and how that shapes the antibody repertoire to vaccination, sometimes called Original Antigenic Sin or antigenic imprinting. Whilst animal models can have a much more defined exposure history, they lack a human B cell repertoire. Transgenic mice with the complete human immunoglobulin locus enable studies of controlled infection history leading to human-like antibody evolution. Here we evaluated responses to influenza in the Intelliselect Transgenic mouse (the Kymouse). We show the Kymouse is susceptible to disease following infection with either H1N1, H3N2 or B/Yam influenza viruses and that it induces a robust binding and neutralising antibody response to all three strains of influenza virus. This study demonstrates that human B cell repertoire mice can be used for influenza virus studies, providing a tool for further interrogation of the antibody response.