SPECIAL: Professor Hisashi Arase from Osaka University and his team found that infection with the virus produces not only neutralizing antibodies that prevent infection, but also antibodies that enhance infection. The article published in cell, and watch:
In English:
Antibodies that enhance the SARS-CoV-2 infection (Arase Lab, in Cell)
A research group led by Professor Hisashi Arase at Osaka University find that infection with SARS-CoV-2 produces not only neutralizing antibodies that prevent infection, but also antibodies that enhance infection (infection-enhancing antibodies)
A research group from Osaka University led by Professor Hisashi Arase and consisting of researchers from the Research Institute for Microbial Diseases, the Institute for Protein Research, Immunology Frontier Research Center, the Center for Infectious Diseases, and the Graduate School of Medicine has discovered for the first time that both neutralizing antibodies that protect against infection as well as infection-enhancing antibodies that increase infectivity are produced after infection with SARS-CoV-2 by analyzing antibodies derived from COVID-19 patients.
Antibodies against the receptor binding site (RBD＊1) of the SARS-CoV-2 spike protein play an important function as neutralizing antibodies that suppress SARS-CoV-2 infection by inhibiting its binding to the human receptor, ACE2＊2. On the other hand, the function of antibodies against other sites of the spike protein was unknown.
“We found that when infection-enhancing antibodies bind to a specific site on the spike protein of SARS-CoV-2, the antibodies directly cause a conformational change in the spike protein, resulting in the increased infectivity of SARS-CoV-2. Neutralizing antibodies recognize the RBD, whereas infection-enhancing antibodies recognize specific sites of the N-terminal domain (NTD＊3),” explains Professor Hisashi Arase. “Furthermore, the production of infection-enhancing antibodies attenuated the ability of neutralizing antibodies to prevent infection.”
Higher production of infection-enhancing antibodies was found in patients with severe COVID-19. It was also found that non-infected individuals may have small amounts of infection-enhancing antibodies.
Although the production of infection-enhancing antibodies may be involved in the development of severe disease, further analysis is required to ascertain whether they are actually involved in the exacerbation of infection in the body.
By analyzing the antibody titer of infection-enhancing antibodies, it may be possible to check for people who are prone to severe disease. The results of this research are also important for the development of vaccines that do not induce the production of infection-enhancing antibodies.
“It is important to analyze not only neutralizing antibodies but also infection-enhancing antibodies. In the future, it may be necessary to develop vaccines that do not induce the production of infection-enhancing antibodies, because infection-enhancing antibodies may be more effective against mutant strains in which neutralizing antibodies are not sufficiently effective,” says Professor Hisashi Arase.
Word explanation
＊1： RBD (Receptor Binding Domain)
Receptor Binding Domain of SARS-CoV-2 spike protein binds to ACE2.Closed RBD does not bind to ACE2 but open form of RBD preferentially binds to ACE2. The infectivity enhancing antibodies induce open form of RBD.
＊2： ACE2
Host cell surface receptor for SARS-CoV-2
＊3： NTD (N-Terminal Domain）
N-Terminal Domain is located at N-terminus of spike protein but the function of NTD is not well known.
This article was published in Cell, on May 24, 2021.
Title: “An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies”
Authors: Yafei Liu, Wai Tuck Soh, Jun-ichi Kishikawa, Mika Hirose, Emi E. Nakayama, Songling Li, Miwa Sasai, Tatsuya Suzuki, Asa Tada, Akemi Arakawa, Sumiko Matsuoka, Kanako Akamatsu, Makoto Matsuda, Chikako Ono, Shiho Torii, Kazuki Kishida, Hui Jin, Wataru Nakai, Noriko Arase, Atsushi Nakagawa, Maki Matsumoto, Yukoh Nakazaki, Yasuhiro Shindo, Masako Kohyama, Keisuke Tomii, Koichiro Ohmura, Shiro Ohshima, Toru Okamoto, Masahiro Yamamoto, Hironori Nakagami, Yoshiharu Matsuura Atsushi Nakagawa, Takayuki Kato, Masato Okada, Daron M. Standley, Tatsuo Shioda, Hisashi Arase*（*Corresponding Author, Hisashi Arase）
Links
In Japanese:
コロナ重症化促す「感染増強抗体」発見 阪大、ワクチン開発に一石
5/24(月) 19:03配信
新型コロナウイルス感染症の重症化を促す可能性がある「感染増強抗体」を発見したと、大阪大の荒瀬尚教授（免疫学）らの研究チームが24日、発表した。ウイルス感染やワクチン投与により、感染を防ぐ「中和抗体」が体内にできることが知られているが、今回発見された抗体はそれとは逆に感染性を高める。感染者ごとに重症化リスクを判別できる可能性があるほか、ワクチン開発にも一石を投じそうだ。研究成果は今後、米科学誌「セル」で発表される予定。 【あなたはいつ？ ワクチン接種のスケジュール】 一部のウイルスでは、感染しやすくする抗体が作られ、重症化につながる現象「ADE」（抗体依存性免疫増強）が起こることが知られている。こうした抗体はSARS（重症急性呼吸器症候群）などでは見つかっていたが、新型コロナではわかっていなかった。 荒瀬教授らは、新型コロナの感染者の免疫細胞から得られた76の抗体を解析。新型コロナは表面の突起部分「スパイクたんぱく質」を介して人の細胞にくっついて感染するが、このたんぱく質の「NTD」という部分に作用する抗体に、ウイルスに感染しやすくなる感染増強抗体があることを発見。これが中和抗体の効果を弱めることを突き止めた。中和抗体の量が十分あれば、影響はなかった。 感染者の体内の抗体の差を調べると、特に重症患者で感染増強抗体が多かった。一方、非感染者でも感染増強抗体を持っているケースがあり、感染やワクチン投与によって感染増強抗体が増える可能性がある。どの程度重症化に関わっているかは不明だが、荒瀬教授は「感染増強抗体の量を調べることで、事前に重症化しやすい人かどうか調べることができるかもしれない」と説明する。 既存のワクチンは、現在分かっているウイルス株に対して中和抗体が十分作られるため問題ないが、今後出現する新たな変異株では感染増強抗体の方が強く働く恐れもあるとし、荒瀬教授は「感染増強抗体を増やさないワクチン開発が必要になる可能性もある」と話している。【松本光樹】