Immunity:人抗N1单克隆抗体(mAbs)在体外和体内广泛抑制HxN1病毒

2023年7月27日,来自美国西奈山伊坎医学院Florian Krammer、华盛顿大学医学院Ali H. Ellebedy和斯克里普斯研究所Andrew B. Ward研究组合作在国际学术期刊《免疫》上发表了标题为“Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo. ”的研究成果,发现大流行性H1N1病毒感染诱导的人抗N1单克隆抗体(mAbs)在体外和体内广泛抑制HxN1病毒。

 

据悉,NA是两种流感病毒表面糖蛋白之一,针对它的抗体是一种独立的相关保护。然而,人们目前对NA抗原性的了解是不完整的。

influenza virus

他们描述了2009年H1N1大流行性病毒感染患者的人mAb。两种单抗对2009年前后流行的季节性H1N1病毒以及禽、猪N1s病毒具有广泛的反应性和抑制神经氨酸酶(NA)酶活性。这些单克隆抗体在小鼠中对人H1N1和禽H5N1病毒的致命攻击提供了强有力的保护,并且都靶向NA侧面的一个表位。

 

总之,他们确定了两种具有广泛保护性的NA抗体,它们共享一个新的表位,抑制NA活性,并在小鼠中提供对病毒攻击的保护。他们的工作重申,NA应作为一个靶点纳入未来广泛保护性或通用流感病毒疫苗

 

Highlights

•Discovery of human monoclonal antibodies broadly reactive to influenza virus neuraminidase

Potent NA enzyme inhibition against human, avian, and swine HxN1 influenza viruses

Conserved epitopes identified on the lateral side of N1 neuraminidase by cryo-EM

Robust protection against lethal influenza H1N1 and H5N1 virus challenge in mice

Summary

Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.
文章来源:

Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo. Lena Hansen, Meagan McMahon, Hannah L. Turner et al, DOI: 10.1016/j.immuni.2023.07.004, 最新IF:43.474

 

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