Broadly Reactive Nanobody Targeting the H3 Hemagglutinin of the Influenza A Virus.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-01 DOI:10.32607/actanaturae.27374

D V Shcheblyakov, D V Voronina, I A Favorskaya, I B Esmagambetov, I A Alekseeva, A I Korobkova, E I Ryabova, A A Derkaev, V Yu Kan, A Sh Dzharullaeva, A I Tukhvatulin, A S Bandelyuk, M M Shmarov, D Yu Logunov, A L Gintsburg

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Abstract

Monoclonal antibodies and recombinant antibody fragments are a very promising therapeutic tool to combat infectious diseases. Due to their unique paratope structure, nanobodies (VHHs) hold several advantages over conventional monoclonal antibodies, especially in relation to viral infections. Influenza A viruses (IAVs) remain a major threat to public health. The hemagglutinin (HA) protein is the main protective and immunodominant antigen of IAVs. In this study, three broadly reactive nanobodies (D9.2, E12.2, and D4.2) to H3N2 influenza strains were isolated and Fc-fusion proteins (VHH-Fcs) were obtained and characterized in vitro. This modification improved the nanobodies' binding activity and allowed for their interaction with a wider range of strains. The D9.2-Fc antibody showed a 100% protection rate against mortality in vivo in a mouse lethal model. Furthermore, we demonstrated that the observed protection has to do with Fc-FcγR interactions. These results indicate that D9.2-Fc can serve as an effective antiviral agent against the H3N2 influenza infection.

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针对甲型流感病毒 H3 血凝素的宽反应性纳米抗体。

单克隆抗体和重组抗体片段是抗击传染性疾病的一种非常有前景的治疗工具。与传统的单克隆抗体相比，纳米抗体（VHHs）因其独特的副位点结构而具有一些优势，尤其是在病毒感染方面。甲型流感病毒（IAV）仍然是公共卫生的主要威胁。血凝素（HA）蛋白是 IAV 的主要保护性免疫优势抗原。本研究分离了三种对 H3N2 流感病毒株具有广泛反应性的纳米抗体（D9.2、E12.2 和 D4.2），并获得了 Fc 融合蛋白（VHH-Fcs），对其进行了体外表征。这种改良提高了纳米抗体的结合活性，使它们能与更多的菌株发生作用。在小鼠致死模型中，D9.2-Fc 抗体对体内死亡率的保护率达到了 100%。此外，我们还证明了观察到的保护作用与 Fc-FcγR 相互作用有关。这些结果表明，D9.2-Fc 可以作为一种有效的抗病毒药物来对抗 H3N2 流感病毒感染。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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