Antibodies that enhance SARS-CoV-2 infection―A possible factor for severe COVID-19―
Primary Keyword: Medicine/Health
Additional Keywords: Infectious/Emerging Diseases, Virology, Microbiology

A research group led by Hisashi Arase (IFReC/RIMD/the Center for Infectious Diseases, OsakaUniversity) discovered both neutralizing antibodies that protect against infection as well as infectionenhancing antibodies that increase infectivity are produced after infection with SARS-CoV-2 byanalyzing antibodies derived from COVID-19 patients.
Antibodies against the receptor binding site (RBD) of the SARS-CoV-2 spike protein play an importantfunction as neutralizing antibodies that suppress SARS-CoV-2 infection by inhibiting its binding to thehuman receptor, ACE2. 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 ofSARS-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),” explains
Professor Hisashi Arase. “Furthermore, the production of infection-enhancing antibodies attenuatedthe 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 ofsevere disease, further analysis is required to ascertain whether they are actually involved in theexacerbation of infection in the body.
By analyzing the antibody titer of infection-enhancing antibodies, it may be possible to check forpeople who are prone to severe disease. The results of this research are also important for thedevelopment 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 infectionenhancing antibodies, because infection-enhancing antibodies may be more effective against mutant
strains in which neutralizing antibodies are not sufficiently effective,” says Professor Hisashi Arase.

SARS-CoV-2 infectivity is enhanced upon antibody binding to NTD. (credit: Osaka University)

Summary: Osaka University researchers found that infection with SARS-CoV-2 produces not only
neutralizing antibodies that prevent infection, but also infection-enhancing antibodies. They demonstrated
that the infection-enhancing antibodies enhance the infectivity of SARS-CoV-2 by modulating theconformation of spike protein of SARS-CoV-2. Furthermore, the infection-enhancing antibodies
attenuated the ability of neutralizing antibodies to prevent infection. Their findings will help to developvaccines that do not induce the production of infection-enhancing antibodies.

Journal: Cell
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, SonglingLi, 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, HironoriNakagami, Yoshiharu Matsuura Atsushi Nakagawa, Takayuki Kato, Masato Okada, Daron M.
Standley, Tatsuo Shioda, Hisashi Arase