한빛사논문
연세대학교 의과대학
Sang-Hoon Kim 1 †, Jihye Kim 1 †, Sungmin Jung 2 †, Ji Yun Noh 3 †, Jinnam Kim 4 †, Heedo Park 5, Young Goo Song 4, Kyong Ran Peck 6, Su-Hyung Park 2, Man-Seong Park 5, Jae-Hoon Ko 6 *, Joon Young Song 3 *, Jun Yong Choi 4 *, Min Kyung Jung 1 *, Eui-Cheol Shin 1 2 *
1Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea.
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
3Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul 08308, Republic of Korea.
4Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
5Department of Microbiology, Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
6Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
†These authors contributed equally
*Corresponding authors: correspondence to Jae-Hoon Ko, Joon Young Song, Jun Yong Choi, Min Kyung Jung or Eui-Cheol Shin
Abstract
Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.
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