Kao | Successful Treatment for Coronavirus Disease 2019 in Hamster Models: A Significant Advancement for Clinical Use of VHH Antibodies Administered Nasally

In May 2020, a research group consisting of researchers from The Kitasato Institute, Epsilon Molecular Engineering, Inc., and Kao Corporation announced that they had discovered VHH antibodies^*1that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The group was then joined by researchers from the Department of Organoid Medicine, Sakaguchi Laboratory, Keio University School of Medicine, the Department of Pulmonary Medicine, Keio University School of Medicine, and the National Institute for Physiological Sciences, National Institutes of Natural Sciences. A subsequent study showed that nasal delivery^*2of VHH antibodies inhibited replication of SARS-CoV-2 in infected lungs of hamster models. This effect was also demonstrated in an experiment using human lung–derived alveolar organoids, also called micro-organs. In addition, their analysis using cryo-electron microscopy^*3revealed the binding pattern between SARS-CoV-2 spike proteins and VHH antibodies.
These results showed that the aforementioned VHH antibodies are a potential therapeutic agent for coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. The results also suggested the possibility of nasal delivery of drugs for the treatment of COVID-19, which is a new administration route for COVID-19 treatment that may expand the available treatment options for COVID-19.
These findings were reported in the American scientific journal PLOS Pathogens

(https://doi.org/10.1371/journal.ppat.1009542)^*4

Major achievements of this research:
● Nasal delivery of the discovered VHH antibodies inhibited replication of SARS-CoV-2 in infected lungs of hamster models.
● VHH antibodies are a potential therapeutic agent for COVID-19.
● Nasal delivery as a new administration route for a COVID-19 treatment with potential to expand the available treatment options.

This research was conducted as part of the "Development of Multivalent VHH Antibody Drug for SARS-CoV-2 Infection (COVID-19)," which is supported by the Japan Agency for Medical Research and Development under the Platform Project for Supporting Drug Discovery and Life Science Research.

* 1 VHH antibody: Variable domain of Heavy chain antibody in camelids. A VHH antibody is one-tenth the size of general antibodies. It has recently drawn attention because it is highly stable and can be manufactured at low cost using microorganisms.
* 2 Nasal delivery: A drug administration route in which drugs are absorbed from the nasal mucosa when sprayed into the nostril. It is highly advantageous in terms of ease of administration.
* 3 Whereas specimens that have been dried in a vacuum are used in conventional transmission electron microscopy, specimens that have been flash-frozen in solution are used in cryo-electron microscopy. Therefore, cryo-electron microscopy can visualize the natural morphology of specimens that include water molecules.
* 4 Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model

Authors:
Kei Haga¹, Reiko Takai-Todaka¹, Yuta Matsumura², Chihong Song^3,4, Tomomi Takano⁵, Takuto Tojo⁶, Atsushi Nagami², Yuki Ishida², Hidekazu Masaki⁷, Masayuki Tsuchiya⁷, Toshiki Ebisudani^8,9, Shinya Sugimoto⁸, Toshiro Sato⁸, Hiroyuki Yasuda⁹, Koichi Fukunaga⁹, Akihito Sawada¹, Naoto Nemoto⁷, Kazuyoshi Murata^3,4, Takuya Morimoto², and Kazuhiko Katayama¹

* Lead authors are underlined.

Affiliations:
¹Laboratory of Viral Infection, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University; ²Safety Science Laboratories, Kao Corporation; ³Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences; ⁴National Institute for Physiological Sciences, National Institutes of Natural Sciences; ⁵School of Veterinary Medicine, Kitasato University; ⁶Biological Science Laboratories, Kao Corporation; ⁷Epsilon Molecular Engineering, Inc.; ⁸Department of Organoid Medicine, Sakaguchi Laboratory, Keio University School of Medicine; ⁹Department of Pulmonary Medicine, Keio University School of Medicine