Frontiers in Immun：新研究或可助研制出通用流感疫苗

流感病毒容易变异，因此需要针对当年流行的病毒毒株接种相应的流感疫苗。如果能有一种通用型的流感疫苗，可以对抗不同变种的病毒，将使人们省去很多麻烦。加拿大研究人员的一项最新成果在通用型流感疫苗研制道路上又前进了一步。

来自加拿大不列颠哥伦比亚大学的研究人员在5月8日出版的《免疫学前沿》Frontiers in Immunology杂志上介绍说，2009年流行过H1N1型流感病毒，当时针对这一病毒接种的疫苗能使人体产生一系列抗体，可对抗包括高致病性的H5N1型禽流感病毒在内的多种流感病毒。他们研究发现，这些抗体之所以能够有效对抗多种流感病毒，与这些抗体攻击流感病毒的位置有关。

流感病毒传播的关键是一种名为“血凝素”的表面蛋白质。血凝素就像一朵花，分为头部和梗部。大多数流感疫苗所产生的抗体都是通过与血凝素的头部结合来阻止病毒复制传播的。但流感病毒的一大特性就是快速变异，血凝素的头部也随之不断变化，因此每个流感季都需要不同的疫苗。而2009年H1N1型流感病毒疫苗所产生的抗体却巧妙地选择与血凝素较稳定的“梗部”相结合，使流感病毒失去传播能力，因此可以对抗多种流感病毒。

去年美国研究人员也曾报告说，那些曾感染过2009年H1N1型流感病毒而后痊愈的患者体内产生了强大的抗体，可对抗多种流感病毒。

此次加拿大研究人员对抗体攻击流感病毒的方式进行了更深入研究，将来有望在此基础上研制出通用型流感疫苗。

doi:10.3389/fimmu.2012.00087
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Pandemic H1N1 influenza infection and vaccination in humans induces cross-protective antibodies that target the hemagglutinin stem

C. A. Thomson1†, Y. Wang1†, L. M. Jackson1, M. Olson1, W. Wang1, A. Liavonchanka2,3, L. Keleta4,5, V. Silva6, S. Diederich6, R. B. Jones7, J. Gubbay8,9, J. Pasick10, M. Petric11, François Jean6, V. G. Allen8,9, E. G. Brown4,5, J. M. Rini2,3 and J. W. Schrader1*

Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.