The total influenza vaccine failure of 1947 revisited: Major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic
The total influenza vaccine failure of 1947 revisited: Major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic
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DOI：
10.1073/pnas.162366899
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发表时间：
2002-08-06
影响因子：
11.1
通讯作者：
Cox, N
中科院分区：
文献类型：
--
作者：
Kilbourne, ED;Smith, C;Cox, N
虽然疫苗诱导的对甲型流感病毒的免疫不断受到病毒主要抗原的逐步选择突变(抗原漂移)的挑战，但亚型(例如H1N1)中的病毒株在抗原上是交叉反应的。尽管随着进一步的突变积累，交叉免疫力会减弱，需要频繁更换疫苗株，但较旧的疫苗通常具有部分保护作用。值得注意的是，1947年11次世界大战后的疫情是因为一种以前在1943-44和1944-45赛季有效的疫苗完全失败了。我们对1943年和1947年病毒的血凝素和神经氨酸酶抗原进行了广泛的抗原性鉴定，并对它们的核苷酸和氨基酸序列进行了分析，发现这两年的病毒在抗原性和氨基酸上存在明显的差异。此外，在小鼠模型中，接种1943年的疫苗对感染1947病毒株没有影响。这些发现很重要，因为以前只有在抗原转移的情况下才发现完全缺乏交叉免疫原性，在这种转移中，抗原性新的抗原被人和动物的菌株重新分类，有时会导致大流行。尽管1947年的疫情缺乏大流行性疾病的常见特征，包括死亡率的广泛增加，但它警告说，在没有引入动物病毒抗原的情况下，极端的亚型内抗原变异(如果伴随着疾病严重性的增加)可能会产生大流行性疾病。
Although vaccine-induced immunity to influenza A virus is continually challenged by progressively selected mutations in the virus's major antigens (antigenic drift), virus strains within a subtype (e.g., H1N1) are antigenically cross-reactive. Although cross-immunity diminishes as further mutations accumulate, necessitating frequent changes in vaccine strains, older vaccines are usually partially protective. The post-World War 11 epidemic of 1947 is notable for the total failure of a vaccine previously effective in the 1943-44 and 1944-45 seasons. We have combined extensive antigenic characterization of the hemagglutinin and neuraminidase antigens of the 1943 and 1947 viruses with analysis of their nucleotide and amino acid sequences and have found marked antigenic and amino acid differences in viruses of the two years. Furthermore, in a mouse model, vaccination with the 1943 vaccine had no effect on infection with the 1947 strain. These findings are important, because complete lack of cross-immunogenicity has been found previously only with antigenic shift, in which antigenically novel antigens have been captured by reassortment of human and animal strains, sometimes leading to pandemics. Although the 1947 epidemic lacked the usual hallmarks of pandemic disease, including an extensive increase in mortality, it warns of the possibility that extreme intrasubtypic antigenic variation (if coupled with an increase in disease severity) could produce pandemic disease without the introduction of animal virus antigens.