Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

Shinya Yamamoto; Seiya Yamayoshi; Mutsumi Ito; Yuko Sakai-Tagawa; Ichiro Nakachi; Rie Baba; Shigenobu Kamimoto; Takayuki Ogura; Shigehiro Hagiwara; Hideaki Kato; Hideaki Nakajima; Yoshifumi Uwamino; Kazuma Yagi; Norio Sugaya; Hiroyuki Nagai; Makoto Saito; Eisuke Adachi; Michiko Koga; Takeya Tsutsumi; Calvin Duong; Moe Okuda; Jurika Murakami; Yuri Furusawa; Michiko Ujie; Kiyoko Iwatsuki-Horimoto; Hiroshi Yotsuyanagi; Yoshihiro Kawaoka

doi:10.1016/j.isci.2023.107208

Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

iScience. 2023 Jun 25;26(7):107208. doi: 10.1016/j.isci.2023.107208. eCollection 2023 Jul 21.

Authors

Shinya Yamamoto^{1

2}, Seiya Yamayoshi^{1

3}, Mutsumi Ito¹, Yuko Sakai-Tagawa¹, Ichiro Nakachi⁴, Rie Baba⁴, Shigenobu Kamimoto⁴, Takayuki Ogura⁵, Shigehiro Hagiwara⁶, Hideaki Kato⁷, Hideaki Nakajima⁷, Yoshifumi Uwamino⁸, Kazuma Yagi⁹, Norio Sugaya¹⁰, Hiroyuki Nagai¹¹, Makoto Saito^{2

11}, Eisuke Adachi^{2

11}, Michiko Koga^{2

11}, Takeya Tsutsumi^{2

11}, Calvin Duong¹, Moe Okuda¹, Jurika Murakami¹, Yuri Furusawa¹, Michiko Ujie¹, Kiyoko Iwatsuki-Horimoto¹, Hiroshi Yotsuyanagi^{2

11}, Yoshihiro Kawaoka^{1

3

12

13}

Affiliations

¹ Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
² Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
³ The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan.
⁴ Pulmonary Division, Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Tochigi 321-0974, Japan.
⁵ Department of Emergency and Intensive Care, Saiseikai Utsunomiya Hospital, Tochigi 321-0974, Japan.
⁶ Department of Clinical Laboratory, Saiseikai Utsunomiya Hospital, Tochigi 321-0974, Japan.
⁷ Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Kanagawa 236-0004, Japan.
⁸ Department of Laboratory Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
⁹ Department of Pulmonary Medicine, Keiyu Hospital, Kanagawa 220-8521, Japan.
¹⁰ Department of Pediatrics, Keiyu Hospital, Kanagawa 220-8521, Japan.
¹¹ Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
¹² Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
¹³ The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center, Tokyo 108-8639, Japan.

Abstract

SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes.

Keywords: Immunology; Virology.