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

doi:10.1016/j.isci.2023.105969

Non-Omicron breakthrough infection with higher viral load and longer vaccination-infection interval improves SARS-CoV-2 BA.4/5 neutralization

iScience. 2023 Feb 17;26(2):105969. doi: 10.1016/j.isci.2023.105969. Epub 2023 Jan 13.

Authors

Sho Miyamoto¹, Takeshi Arashiro^{1

2}, Akira Ueno¹, Takayuki Kanno¹, Shinji Saito¹, Harutaka Katano¹, Shun Iida¹, Akira Ainai¹, Seiya Ozono¹, Takuya Hemmi¹, Yuichiro Hirata¹, Saya Moriyama³, Ryutaro Kotaki³, Hitomi Kinoshita⁴, Souichi Yamada⁴, Masaharu Shinkai⁵, Shuetsu Fukushi⁴, Yoshimasa Takahashi³, Tadaki Suzuki⁴

Affiliations

¹ Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
² Center for Surveillance Immunization and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
³ Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
⁴ Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
⁵ Tokyo Shinagawa Hospital, Tokyo 140-8522, Japan.

Abstract

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.

Keywords: Immune response; Immunology; Virology.