Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

Autor: Kayoko Nagata, Daichi Utsumi, Masamitsu N. Asaka, Ryota Maeda, Kotaro Shirakawa, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Yohei Yanagida, Yugo Kawai, Kei Sato, Yutaro Yamaoka, Kei Miyakawa, Akihide Ryo, Yasuhiro Yasutomi, Akihiro Imura, Akifumi Takaori-Kondo
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Communications Medicine. 2
ISSN: 2730-664X
Popis: BACKGROUND: SARS-CoV-2 Omicron variants are highly resistant to vaccine-induced immunity and human monoclonal antibodies. METHODS: We previously reported that two nanobodies, P17 and P86, potently neutralize SARS-CoV-2 VOCs. In this study, we modified these nanobodies into trimers, called TP17 and TP86 and tested their neutralization activities against Omicron BA.1 and subvariant BA.2 using pseudovirus assays. Next, we used TP17 and TP86 nanobody cocktail to treat ACE2 transgenic mice infected with lethal dose of SARS-CoV-2 strains, original, Delta and Omicron BA.1. RESULTS: Here, we demonstrate that a novel nanobody TP86 potently neutralizes both BA.1 and BA.2 Omicron variants, and that the TP17 and TP86 nanobody cocktail broadly neutralizes in vitro all VOCs as well as original strain. Furthermore, intratracheal administration of this nanobody cocktail suppresses weight loss and prolongs survival of human ACE2 transgenic mice infected with SARS-CoV-2 strains, original, Delta and Omicron BA.1. CONCLUSIONS: Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice.
新型コロナウイルスを中和するアルパカ抗体 --マウス実験で有効性を確認--. 京都大学プレスリリース. 2023-02-17.
Databáze: OpenAIRE
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