Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters

• Main Authors: Rouers, Angeline, Wong, Nathan, Goh, Yun Shan, Torres-Ruesta, Anthony, Tay, Matthew Zirui, Chang, Zi Wei, Fong, Siew-Wai, Neo, Vanessa, Kam, Isaac Kai Jie, Yeo, Nicholas Kim-Wah, Huang, Yuling, Loh, Chiew Yee, Hor, Pei Xiang, Wong, Joel Xu En, Tan, Yong Jie, Macary, Paul A., Qian, Xinlei, Bei, Wang, Ngoh, Eve Zi Xian, Salleh, Siti Nazihah Mohd, Wang, Cheng-I, Poh, Xuan Ying, Rao, Suma, Chia, Po Ying, Ong, Sean W. X., Lee, Tau Hong, Lin, Ray J. H., Lim, Clarissa, Teo, Jefanie, Ren, Ee Chee, Lye, David C., Young, Barnaby Edward, Ng, Lisa F. P., Renia, Laurent
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Medicine; B Cell; Humoral Immunity
• Online Access: https://hdl.handle.net/10356/164318
• Institution: Nanyang Technological University

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.