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