Non-Omicron breakthrough infection with higher viral load and longer vaccination-infection interval improves SARS-CoV-2 BA.4/5 neutralization
Sho Miyamoto,
Takeshi Arashiro,
Akira Ueno,
Takayuki Kanno,
Shinji Saito,
Harutaka Katano,
Shun Iida,
Akira Ainai,
Seiya Ozono,
Takuya Hemmi,
Yuichiro Hirata,
Saya Moriyama,
Ryutaro Kotaki,
Hitomi Kinoshita,
Souichi Yamada,
Masaharu Shinkai,
Shuetsu Fukushi,
Yoshimasa Takahashi,
Tadaki Suzuki
Affiliations
Sho Miyamoto
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Takeshi Arashiro
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Center for Surveillance Immunization and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Akira Ueno
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Takayuki Kanno
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Shinji Saito
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Harutaka Katano
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Shun Iida
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Akira Ainai
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Seiya Ozono
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Takuya Hemmi
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Yuichiro Hirata
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Saya Moriyama
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Ryutaro Kotaki
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Hitomi Kinoshita
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Souichi Yamada
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Masaharu Shinkai
Tokyo Shinagawa Hospital, Tokyo 140-8522, Japan
Shuetsu Fukushi
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Yoshimasa Takahashi
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Tadaki Suzuki
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Corresponding author
Summary: The immune responses to SARS-CoV-2 variants in COVID-19 cases are influenced by various factors including pre-existing immunity via vaccination and prior infection. Elucidating the drivers for upgrading neutralizing activity to SARS-CoV-2 in COVID-19 cases with pre-existing immunity will aid in improving COVID-19 booster vaccines with enhanced cross-protection against antigenically distinct variants, including the Omicron sub-lineage BA.4/5. This study revealed that the magnitude and breadth of neutralization activity to SARS-CoV-2 variants after breakthrough infections are determined primarily by upper respiratory viral load and vaccination-infection time interval. Extensive neutralizing breadth, covering even the most antigenically distant BA.4/5, was observed in cases with higher viral load and longer time intervals. Antigenic cartography depicted a critical role of the time interval in expanding the breadth of neutralization to SARS-CoV-2 variants. Our results illustrate the importance of dosing interval optimization as well as antigen design in developing variant-proof booster vaccines.
