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2022/01/17

  • News Release
  • R&D

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*1 that 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*2 of 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*3 revealed 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

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 Song3,4, Tomomi Takano5, Takuto Tojo6, Atsushi Nagami2, Yuki Ishida2, Hidekazu Masaki7, Masayuki Tsuchiya7, Toshiki Ebisudani8,9, Shinya Sugimoto8, Toshiro Sato8, Hiroyuki Yasuda9, Koichi Fukunaga9, Akihito Sawada1, Naoto Nemoto7, Kazuyoshi Murata3,4, 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

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