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Adv. Sci., 27 February 2025 | https://doi.org/10.1002/advs.202409919 Pan-Variant SARS-CoV-2 Vaccines Induce Protective Immunity by Targeting Conserved Epitopes

Masaud Shah ^{1 2 †}, Sung Ung Moon ^{1 †}, Ji-Yon Shin^{1 3}, Ji-Hye Choi ^{1 2}, Doyoon Kim ², Hyun Goo Woo ^{1 2 4 *}

¹Department of Physiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
²Ajou Translational Omics Center (ATOC), Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, 16499, Republic of Korea.
³AI-Superconvergence KIURI Translational Research Center, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
⁴Department of Biomedical Science, Graduate School, Ajou University, Suwon, 16499, Republic of Korea.

^†These authors contributed equally
^*Corresponding author: correspondence to Hyun Goo Woo

Abstract

The development of a globally effective COVID-19 vaccine faces significant challenges, particularly in redirecting the B-cell response from immunodominant yet variable regions of viral proteins toward their conserved domains. To address this, an integrated strategy is implemented that combines classical B-cell epitope prediction with protein-antibody cluster docking and antibody titer analysis from 30 vaccinated and convalescent individuals. This approach yields stable immunodominant and immunoprevalent B-cell epitopes capable of eliciting robust antibody responses in BALB/c mice and effectively neutralizing pseudoviruses expressing the Spike protein of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron. To achieve a broader T-cell-based immune response, promiscuous T-cell epitopes are identified by integrating classical T-cell epitope predictions, differential scanning fluorimetry, and peptide-MHC structural analysis. Unique peptides with conserved MHC-anchoring residues are identified, enabling binding to a spectrum of MHC-I and MHC-II haplotypes. These peptides elicit strong interferon gamma responses in human peripheral blood mononuclear cells and demonstrate cross-species efficacy by activating both CD4+ and CD8+ T-cells in BALB/c mice. Collectively, these findings highlight the significance of innovative vaccine strategies targeting immunodominant/immunoprevalent B-cell and promiscuous T-cell epitopes to drive broad and robust humoral and cellular immune responses against a wide range of SARS-CoV-2 variants.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-03-04)
연구진국내 연구진
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