Decreased memory B cell frequencies in COVID-19 delta variant vaccine breakthrough infection

• Main Authors: Tay, Matthew Zirui, Rouers, Angeline, Fong, Siew-Wai, Goh, Yun Shan, Chan, Yi-Hao, Chang, Zi Wei, Xu, Weili, Tan, Chee Wah, Chia, Wan Ni, Torres-Ruesta, Anthony, Siti Naqiah Amrun, Huang, Yuling, Hor, Pei Xiang, Loh, Chiew Yee, Yeo, Nicholas Kim-Wah, Wang, Bei, Ngoh, Eve Zi Xian, Siti Nazihah Mohd Salleh, Chavatte, Jean-Marc, Lim, Alicia Jieling, Maurer-Stroh, Sebastian, Wang, Lin-Fa, Lin, Raymond Valentine Tzer Pin, Wang, Cheng-I, Tan, Seow-Yen, Young, Barnaby Edward, Leo, Yee Sin, Lye, David C., Renia, Laurent, Ng, Lisa F. P.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Medicine; Correlate of Risk; COVID-19
• Online Access: https://hdl.handle.net/10356/163077
• Institution: Nanyang Technological University

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.