Infectivity-enhancing site on SARS-CoV-2 spike protein targeted by COVID-19 patient antibodies

 Yafei Liu, Wai Tuck Soh, Asa Tada, Akemi Arakawa, Sumiko Matsuoka, Emi E Nakayama, Songling Li, Chikako Ono, Shiho Torii, Kazuki Kishida, Hui Jin, Wataru Nakai, Noriko Arase, Atsushi Nakagawa, Yasuhiro Shindo, Masako Kohyama, Hironori Nakagami, Keisuke Tomii, Koichiro Ohmura, Shiro Ohshima, Masato Okada,  

View ORCID ProfileYoshiharu Matsuura, Daron M Standley, Tatsuo Shioda,  View ORCID ProfileHisashi Arase

doi: https://doi.org/10.1101/2020.12.18.423358

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2020.12.18.423358v1.full.pdf

Abstract

SARS-CoV-2 infection causes severe symptoms in a subset of patients, suggesting the presence of certain unknown risk factors. Although antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike have been shown prevent SARS-CoV-2 infection, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from COVID-19 patients, and found that some of antibodies against the N-terminal domain (NTD) dramatically enhanced the binding capacity of the spike protein to ACE2, and thus increased SARS-CoV2 infectivity. Surprisingly, mutational analysis revealed that all the infectivity-enhancing antibodies recognized a specific site on the surface of the NTD. The antibodies against this infectivity-enhancing site were detected in all samples of hospitalized COVID-19 patients in the study. However, the ratio of infectivity-enhancing antibodies to neutralizing antibodies differed among patients. Furthermore, the antibodies against the infectivity-enhancing site were detected in 3 out of 48 uninfected donors, albeit at low levels. These findings suggest that the production of antibodies against SARS-CoV-2 infectivity-enhancing site could be considered as a possible exacerbating factors for COVID-19 and that a spike protein lacking such antibody epitopes may be required for safe vaccine development, especially for individuals with pre-existing enhancing antibodies.

Competing Interest Statement

Osaka Univ. and HuLA immune Inc. filed a patent related to this study. YL, YS, and HA are inventors of the patent. YS is an employee of HuLA immune Inc. HA and YS are stock holders of HuLA immune.

https://www.biorxiv.org/content/10.1101/2020.12.18.423358v1