Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 2012 Aug;86(16):8625-33. doi: 10.1128/JVI.00147-12. Epub 2012 Jun 6.
Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
与季节性流感病毒相比，2009 年大流行的 H1N1（pH1N1）病毒在儿童和青年中造成了更高的发病率和死亡率。60 岁以上的人显示出更高的交叉反应性 pH1N1 抗体流行率，表明他们以前曾接触过与 pH1N1 病毒具有抗原相关性的流感病毒或疫苗。为了定义这种交叉反应性的基础，雪貂感染了具有不同抗原距离的 H1N1 病毒，这些病毒在 20 世纪 30 年代（阿拉斯加/35）、40 年代（蒙茅斯堡/47）、50 年代（沃伦堡/50）和 90 年代（新喀里多尼亚/99）流行，6 周后用 2009 年 pH1N1 病毒进行攻毒。用同源 CA/09 或新泽西/76（NJ/76）病毒进行初次免疫的雪貂作为阳性对照，而流感 B 病毒作为阴性对照，不应能对流感 A 病毒感染提供交叉保护。用 AK/35、FM/47 和 NJ/76 进行初次免疫的雪貂观察到对攻毒病毒在呼吸道中的复制有显著的保护作用；FW/50 初次免疫的雪貂显示出保护作用降低，而 NC/99 初次免疫的雪貂则没有得到保护。AK/35、FM/47 和 FW/50 的血凝素（HA）在糖基化位点的存在方面存在差异。我们发现，FW/50 观察到的保护效力丧失与特定糖基化位点的存在有关。我们的结果表明，HA 发生的变化发生在 1947 年至 1950 年之间，使得先前的感染不能再预防 2009 年 pH1N1 感染。这为 60 岁以上人群在 2009 年 H1N1 大流行期间观察到的血清学交叉保护的性质提供了机制上的理解。
