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

• Published in: iScience Vol. 26; no. 2; p. 105969
• Main Authors: Miyamoto, Sho, Arashiro, Takeshi, Ueno, Akira, Kanno, Takayuki, Saito, Shinji, Katano, Harutaka, Iida, Shun, Ainai, Akira, Ozono, Seiya, Hemmi, Takuya, Hirata, Yuichiro, Moriyama, Saya, Kotaki, Ryutaro, Kinoshita, Hitomi, Yamada, Souichi, Shinkai, Masaharu, Fukushi, Shuetsu, Takahashi, Yoshimasa, Suzuki, Tadaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.02.2023; The Authors; Elsevier
• Subjects: Immune response; Immunology; Virology; Immunology; Immune response; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.105969

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. [Display omitted] •Neutralization potency to SARS-CoV-2 after breakthrough infection is diverse•Increased neutralizing activity is associated with high airway viral replication•Neutralization breadth is associated with longer vaccination-infection interval Immunology; Immune response; Virology.