Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.
Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.
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DOI：
10.1016/j.cell.2018.03.030
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发表时间：
2018-04-05
期刊：
影响因子：
64.5
通讯作者：
Wilson PC
中科院分区：
文献类型：
--
作者：
Chen YQ;Wohlbold TJ;Zheng NY;Huang M;Huang Y;Neu KE;Lee J;Wan H;Rojas KT;Kirkpatrick E;Henry C;Palm AE;Stamper CT;Lan LY;Topham DJ;Treanor J;Wrammert J;Ahmed R;Eichelberger MC;Georgiou G;Krammer F;Wilson PC
血凝素（HA）和神经氨酸酶（NA）糖蛋白的抗体是抵抗流感病毒感染的主要介质。在这里，我们报告说，目前的流感疫苗显示关键NA表位差，很少诱导NA反应性B细胞。相反，流感病毒感染以接近（H1N1）或超过（H3 N2）HA反应性B细胞的频率诱导NA反应性B细胞。NA-反应性抗体显示跨越人类中甲型流感病毒循环的整个历史的广泛结合活性，包括H1N1和H3 N2亚型的原始大流行毒株。这些抗体强烈地抑制NA的酶活性，包括奥司他韦抗性变体，并在体内提供强烈的预防性保护，包括针对禽类H5 N1病毒。当用于治疗时，NA反应性抗体保护小鼠免受致命流感病毒攻击，甚至在感染后48小时。这些发现强烈表明，流感疫苗应进行优化，以改善NA的靶向，以针对不同的流感毒株提供持久和广泛的保护。目前的流感疫苗主要产生靶向病毒血凝素（HA）的抗体。然而，在自然感染期间，身体也会产生针对病毒神经氨酸酶（NA）的抗体。这些NA抗体可以提供稳健和广泛的保护，并且可以通过新的疫苗策略潜在地诱导免疫，或用于治疗。
Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection in vivo, including against avian H5N1 viruses. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48-hours post-infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains. Current influenza vaccines predominantly produce antibodies targeting the viral hemagglutinin (HA). However, during natural infection the body also produces antibodies targeting the viral neuraminidase (NA). These NA antibodies can provide robust and broad protection and could potentially be elicited prophylactically, via new vaccine strategies, or used therapeutically.
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DOI：
10.15585/mmwr.mm6606a3
发表时间：
2017-02-17
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Flannery B;Chung JR;Thaker SN;Monto AS;Martin ET;Belongia EA;McLean HQ;Gaglani M;Murthy K;Zimmerman RK;Nowalk MP;Jackson ML;Jackson LA;Foust A;Sessions W;Berman L;Spencer S;Fry AM
通讯作者：
Fry AM
影响因子：
30.5
作者：
Nachbagauer R;Choi A;Hirsh A;Margine I;Iida S;Barrera A;Ferres M;Albrecht RA;García-Sastre A;Bouvier NM;Ito K;Medina RA;Palese P;Krammer F
通讯作者：
Krammer F
影响因子：
4.9
作者：
Nguyen, Ha T.;Sheu, Tiffany G.;Gubareva, Larisa V.
通讯作者：
Gubareva, Larisa V.
影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
影响因子：
7.6
作者：
Doyle, Tracey M.;Hashem, Anwar M.;Li, Xuguang
通讯作者：
Li, Xuguang