Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
J Immunol. 2010 Aug 1;185(3):1642-9. doi: 10.4049/jimmunol.1000091. Epub 2010 Jun 28.
The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50-60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse-adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine-origin 2009 H1N1 influenza virus.
2009 年 H1N1 流感大流行是 21 世纪的第一次大流行。流行病学数据显示，在所有感染 H1N1 病毒的人中，<5%的人年龄超过 51 岁。有趣的是，在未感染者中，33%的>60 岁的人对 2009 年 H1N1 病毒有预先存在的中和抗体。这一发现表明，50-60 年前流行的流感株可能对猪源 2009 年 H1N1 流感病毒提供交叉保护。为了验证这一点，我们确定了 1930 年至 2000 年在人群中流行的代表性 H1N1 流感病毒诱导对大流行猪源 H1N1 病毒 A/California/04/09 产生交叉反应和交叉保护的能力。我们表明，用 1947 年病毒 A/FM/1/47 或 1934 年病毒 A/PR/8/34 暴露小鼠，诱导了强大的交叉保护免疫反应，这些小鼠免受致死性适应的 A/California/04/09 H1N1 病毒的挑战。相反，我们观察到用 2009 年 H1N1 病毒暴露的小鼠免受致死性适应的 1947 年或 1934 年 H1N1 病毒的挑战的保护。此外，暴露于 2009 年 H1N1 病毒诱导了对 H1N1 以及 H3N2 流感病毒的广泛交叉反应性。最后，我们表明用较旧的 H1N1 病毒，特别是 A/FM/1/47 ，进行疫苗接种可提供针对 2009 年大流行 H1N1 病毒的保护免疫。总之，我们的数据为老年人对 2009 年 H1N1 爆发的易感性降低提供了解释，并证明用 1950 年前的流感株进行疫苗接种可对大流行的猪源 2009 年 H1N1 流感病毒提供交叉保护。
