Early T cell and binding antibody responses are associated with COVID-19 RNA vaccine efficacy onset

Kalimuddin, Shirin; Tham, Christine Y.L.; Qui, Martin; de Alwis, Ruklanthi; Sim, Jean X.Y.; Lim, Joey M.E.; Tan, Hwee-Cheng; Syenina, Ayesa; Zhang, Summer L.; Le Bert, Nina; Tan, Anthony T.; Leong, Yan Shan; Yee, Jia Xin; Ong, Eugenia Z.; Ooi, Eng Eong; Bertoletti, Antonio; Low, Jenny G.

BACKGROUND: RNA vaccines against coronavirus disease 2019 (COVID-19) have demonstrated ∼95% efficacy in phase III clinical trials. Although complete vaccination consisted of 2 doses, the onset of protection for both licensed RNA vaccines was observed as early as 12 days after a single dose. The adaptive immune response that coincides with this onset of protection could represent the necessary elements of immunity against COVID-19. METHODS: Serological and T cell analysis was performed in a cohort of 20 healthcare workers after receiving the first dose of the Pfizer/BioNTech BNT162b2 vaccine. The primary endpoint was the adaptive immune responses detectable at days 7 and 10 after dosing. FINDINGS: Spike-specific T cells and binding antibodies were detectable 10 days after the first dose of the vaccine, in contrast to receptor-blocking and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) neutralizing antibodies, which were mostly undetectable at this early time point. CONCLUSIONS: Our findings suggest that early T cell and binding antibody responses, rather than either receptor-blocking or virus neutralizing activity, induced early protection against COVID-19. FUNDING: The study was funded by a generous donation from The Hour Glass to support COVID-19 research.