Ahmed Muhammad S, Jacques Laura C, Mahallawi Waleed, Ferrara Francesca, Temperton Nigel, Upile Nav, Vaughan Casey, Sharma Ravi, Beer Helen, Hoschler Katja, McNamara Paul S, Zhang Qibo
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, United Kingdom.
Antiviral Res. 2015 Feb;114:106-12. doi: 10.1016/j.antiviral.2014.12.008. Epub 2014 Dec 13.
2009 H1N1 pandemic influenza (A(H1N1)pdm09) virus infected large numbers of people worldwide. Recent studies suggest infection with A(H1N1)pdm09 virus elicited cross-reactive anti-hemagglutinin (HA) memory B cell response to conserved regions of HA. However, the breadth and magnitude of cross-reactive immunity in children and adults following A(H1N1)pdm09 infection are unknown.
We investigated serum anti-HA immunity to a number of group-1 and -2 viruses in children and adults using hemagglutination inhibition (HAI), enzyme-linked immunosorbent assay and virus neutralization assay.
Applying hemagglutination inhibition (HAI) titers ⩾40 against A(H1N1)pdm09 as threshold of sero-positivity, we observed significantly higher levels of anti-HA antibodies to a number of virus subtypes, including those neutralizing H5N1, in subjects with HAI titer ⩾40 than those with HAI <40. Adults demonstrated broader and stronger cross-reactive anti-HA antibodies than children, including cross-reactive anti-HA1 and -HA2 antibodies. By comparison, individuals with serologic evidence of recent exposure to seasonal H1N1 or H3N2 did not show such broad cross-reactive immunity.
Our results suggest individuals exposed to A(H1N1)pdm09 virus developed a broad and age-associated cross-reactive anti-HA immunity which may have important implications for future vaccination strategies to enable protection against a broader range of influenza viruses.
2009年甲型H1N1大流行性流感病毒（A(H1N1)pdm09）感染了全球大量人群。最近的研究表明，感染A(H1N1)pdm09病毒会引发针对血凝素（HA）保守区域的交叉反应性抗HA记忆B细胞反应。然而，A(H1N1)pdm09感染后儿童和成人交叉反应性免疫的广度和强度尚不清楚。
我们使用血凝抑制试验（HAI）、酶联免疫吸附测定和病毒中和试验，研究了儿童和成人血清中针对多种1组和2组病毒的抗HA免疫情况。
以针对A(H1N1)pdm09的血凝抑制（HAI）效价⩾40作为血清阳性阈值，我们观察到HAI效价⩾40的受试者中，针对多种病毒亚型（包括中和H5N1的亚型）的抗HA抗体水平显著高于HAI<40的受试者。成人表现出比儿童更广泛、更强的交叉反应性抗HA抗体，包括交叉反应性抗HA1和抗HA2抗体。相比之下，近期有季节性H1N1或H3N2暴露血清学证据的个体并未表现出如此广泛的交叉反应性免疫。
我们的结果表明，接触A(H1N1)pdm09病毒的个体产生了广泛的、与年龄相关的交叉反应性抗HA免疫，这可能对未来的疫苗接种策略具有重要意义，有助于预防更广泛的流感病毒。
