Min Kyung Jung^1,7, Seong Dong Jeong^1,7, Ji Yun Noh^2,3,7, Dong-Uk Kim², Sungmin Jung², Joon Young Song^3,*, Hye Won Jeong ^2,4,5,*, Su-Hyung Park ^2,6,* and Eui-Cheol Shin ^1,2,*

¹The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science, Daejeon, Republic of Korea. ²Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. ³Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. ⁴Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea. ⁵Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea. ⁶The Center for Epidemic Preparedness, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. ⁷These authors contributed equally: Min Kyung Jung, Seong Dong Jeong, Ji Yun Noh.

^*Corresponding author.

The Omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) extensively escapes neutralizing antibodies elicited by SARS-CoV-2 infection or vaccination. In the present study, we investigated whether BNT162b2 messenger RNA vaccine-induced memory T cells functionally respond to the Omicron spike protein. Experiments were performed using samples from healthcare workers who were immunized with two or three doses of the BNT162b2 mRNA vaccine and individuals with prior SARS-CoV-2 infection who were immunized with two doses of the BNT162b2 vaccine. Vaccine-induced memory T cells exhibited substantial responses to the Omicron spike protein, with no difference between healthcare workers with two versus three vaccine doses. In individuals with prior infection, two-dose vaccination robustly boosted memory T cells that responded to the Omicron spike protein and the SARS-CoV-2 wild-type (lineage B) spike protein. Importantly, polyfunctionality was preserved in vaccine-induced memory T cells responding to the Omicron spike protein. The present findings indicate that BNT162b2-induced memory T cells substantially respond to the Omicron variant with preserved polyfunctionality.