Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants.
Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants.
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DOI：
10.3389/fimmu.2022.995412
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wang, Yang
中科院分区：
文献类型：
--
作者：
Li, Qi;Humphries, Fiachra;Girardin, Roxie C.;Wallace, Aaron;Ejemel, Monir;Amcheslavsky, Alla;McMahon, Conor T.;Schiller, Zachary A.;Ma, Zepei;Cruz, John;Dupuis, Alan P.;Payne, Anne F.;Maryam, Arooma;Yilmaz, Nese Kurt;McDonough, Kathleen A.;Pierce, Brian G.;Schiffer, Celia A.;Kruse, Andrew C.;Klempner, Mark S.;Cavacini, Lisa A.;Fitzgerald, Katherine A.;Wang, Yang
关键词：
抗COVID抗体治疗剂已经开发出来，但由于其成本高且无法从新出现的变体中中和而未被广泛使用。在这里，我们描述了VHH-IgA 1.1的发展，一种纳米抗体伊加融合分子作为一种可吸入的，负担得起的和侵入性较小的预防和治疗SARS-CoV-2 Omicron变异体的治疗。VHH-IgA 1.1识别SARS-CoV-2刺突蛋白受体结合结构域（RBD）的保守表位，并有效中和主要的全球SARS-CoV-2相关变体（VOC），包括Omicron变体及其亚系BA.1.1、BA.2和BA.2.12.1。与IgG Fc融合构建体相比，VHH-IgA 1.1对Omicron变体的作用也更强，这表明了伊加介导的粘膜保护对Omicron感染的重要性。在攻击之前或之后鼻内施用VHH-IgA 1.1赋予感染SARS-CoV-2 VOC的K18-ACE 2转基因小鼠免受严重呼吸道疾病的显著保护。更重要的是，对于成本有效的生产，在巴斯德毕赤酵母中产生的VHH-IgA 1.1具有与哺乳动物产生的抗体相当的效力。我们的研究表明，鼻内给药的affordable产生的VHH-IgA融合蛋白提供了有效的粘膜免疫对感染的SARS-CoV-2，包括新出现的变种。
Anti-COVID antibody therapeutics have been developed but not widely used due to their high cost and escape of neutralization from the emerging variants. Here, we describe the development of VHH-IgA1.1, a nanobody IgA fusion molecule as an inhalable, affordable and less invasive prophylactic and therapeutic treatment against SARS-CoV-2 Omicron variants. VHH-IgA1.1 recognizes a conserved epitope of SARS-CoV-2 spike protein Receptor Binding Domain (RBD) and potently neutralizes major global SARS-CoV-2 variants of concern (VOC) including the Omicron variant and its sub lineages BA.1.1, BA.2 and BA.2.12.1. VHH-IgA1.1 is also much more potent against Omicron variants as compared to an IgG Fc fusion construct, demonstrating the importance of IgA mediated mucosal protection for Omicron infection. Intranasal administration of VHH-IgA1.1 prior to or after challenge conferred significant protection from severe respiratory disease in K18-ACE2 transgenic mice infected with SARS-CoV-2 VOC. More importantly, for cost-effective production, VHH-IgA1.1 produced in Pichia pastoris had comparable potency to mammalian produced antibodies. Our study demonstrates that intranasal administration of affordably produced VHH-IgA fusion protein provides effective mucosal immunity against infection of SARS-CoV-2 including emerging variants.
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