Sullivan John S, Selleck Paul W, Downton Teena, Boehm Ingrid, Axell Anna-Maree, Ayob Yasmin, Kapitza Natalie M, Dyer Wayne, Fitzgerald Anna, Walsh Bradley, Lynch Garry W
Biosafety, Immunobiology, Global Health and Pandemic Infections Research, Central Clinical School, Faculty of Medicine, The University of Sydney, Camperdown, NSW 2006, Australia.
J Mol Genet Med. 2009 Dec 23;3(2):217-24. doi: 10.4172/1747-0862.1000038.
With antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations. Examination of IVIGs from European and South East-Asian (Malaysian) blood donor populations further reveal heterosubtypic antibodies to H5N1 in humans from different global regions. Importantly these protect against highly pathogenic avian H5N1 infection in vitro, albeit at low titres of inhibition. Although there were qualitative and quantitative differences in binding and protection between globally different formulations, the heterosubtypic antibody activities for the respective IVIGs were in general quite similar. Of particular note because of the relative geographic proximity to the epicentre of H5N1 and the majority of human infections, was the similarity in the antibody binding responses between IVIGs from the Malayan peninsula, Europe and Australia. These findings highlight the value of employing IVIGs for the study of herd immunity, and particularly heterosubtypic antibody responses to viral antigens such as those conserved between circulating human influenzas and emerging influenza strains such as H5N1. They also open a window into a somewhat ill defined arena of antibody immunity, namely heterosubtypic immunity.
由于具有抗原性的新型流行性和大流行性流感毒株一直有可能出现，因此了解从接触流行的人类流感中获得的异源亚型抗体是否存在并能预防新出现的毒株至关重要。我们对从未感染过的人群（澳大利亚人）获得的静脉注射免疫球蛋白（IVIG）进行的研究，使我们能够揭示与H5N1发生交叉反应的异源亚型流感抗体。我们现在将这些发现扩展到澳大利亚供体人群，纳入来自北半球不同人群的IVIG制剂。对来自欧洲和东南亚（马来西亚）献血者人群的IVIG进行检测，进一步揭示了来自不同全球区域的人类体内存在针对H5N1的异源亚型抗体。重要的是，这些抗体在体外能预防高致病性禽流感H5N1感染，尽管抑制效价较低。尽管全球不同制剂在结合和保护方面存在定性和定量差异，但各自IVIG的异源亚型抗体活性总体上相当相似。特别值得注意的是，由于马来西亚半岛、欧洲和澳大利亚的IVIG在抗体结合反应上具有相似性，而马来西亚半岛相对靠近H5N1疫情中心且大多数人类感染发生在此。这些发现凸显了使用IVIG研究群体免疫的价值，尤其是对病毒抗原的异源亚型抗体反应，例如在流行的人类流感和诸如H5N1等新出现的流感毒株之间保守的那些抗原。它们还为抗体免疫中一个定义不太明确的领域——即异源亚型免疫，打开了一扇窗口。
