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

• Published in: Communications medicine Vol. 2; no. 1; pp. 152 - 6
• Main Authors: Nagata, Kayoko, Utsumi, Daichi, Asaka, Masamitsu N., Maeda, Ryota, Shirakawa, Kotaro, Kazuma, Yasuhiro, Nomura, Ryosuke, Horisawa, Yoshihito, Yanagida, Yohei, Kawai, Yugo, Sato, Kei, Yamaoka, Yutaro, Miyakawa, Kei, Ryo, Akihide, Yasutomi, Yasuhiro, Imura, Akihiro, Takaori-Kondo, Akifumi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2022; Springer Nature B.V; Nature Portfolio
• Subjects: 631/1647/664/2228; 631/326/596/4130; 631/61/338/22/1295; 64/60; 692/308/153; 692/699/255/2514; 82/1; Antibodies; Coronaviruses; COVID-19; Drug administration; Drug therapy; Experiments; Intubation; Laboratory animals; Medicine; Medicine & Public Health; Severe acute respiratory syndrome coronavirus 2; Viral infections
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-022-00213-5

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. Plain language summary Antibodies are made by the immune system to identify and inactivate infectious agents such as viruses. Alpacas produce a simple type of antibodies called nanobodies. We previously developed two nanobodies named P17 and P86 that inactivate SARS-CoV-2. In this study, we modified these nanobodies to create two nanobodies named TP17 and TP86. The cocktail of these nanobodies inactivated different types of SARS-CoV-2 viruses including Omicron BA.1 and BA.2. The cocktail also prolonged survival of mice infected with lethal doses of SARS-CoV-2. Nagata, Utsumi, Asaka, Maeda et al. describe a nanobody, TP86, that potently neutralizes both BA.1 and BA.2 Omicron SARS-CoV-2 variants, and, when combined with the TP17 nanobody, broadly neutralizes all SARS-CoV-2 variants. This nanobody cocktail also suppresses weight loss and prolongs survival of SARS-CoV-2 infected human ACE2 transgenic mice.