Long-term analysis of humoral responses and spike-specific T cell memory to Omicron variants after different COVID-19 vaccine regimens

Chia-Lo Ho; Li-Chen Yen; Hong-Wei Huang; Chun-Chi Lu; Yi-Jen Hung; Ching-Len Liao; Chin-Mao Hung; Kuo-Chou Chiu

doi:10.3389/fimmu.2024.1340645

Long-term analysis of humoral responses and spike-specific T cell memory to Omicron variants after different COVID-19 vaccine regimens

Front Immunol. 2024 Mar 12:15:1340645. doi: 10.3389/fimmu.2024.1340645. eCollection 2024.

Authors

Chia-Lo Ho¹, Li-Chen Yen², Hong-Wei Huang², Chun-Chi Lu³, Yi-Jen Hung⁴, Ching-Len Liao^{2

5}, Chin-Mao Hung⁶, Kuo-Chou Chiu^{7

8

9}

Affiliations

¹ Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
² Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
³ Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁴ Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁵ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
⁶ Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
⁷ Division of General Dentistry, Taichung Armed Forces General Hospital, Taichung, Taiwan.
⁸ School of Dentistry, China Medical University, Taichung, Taiwan.
⁹ School of Dentistry, National Defense Medical Center, Taipei, Taiwan.

Abstract

Background: The emergence of SARS-CoV-2 variants has raised concerns about the sustainability of vaccine-induced immunity. Little is known about the long-term humoral responses and spike-specific T cell memory to Omicron variants, with specific attention to BA.4/5, BQ.1.1, and XBB.1.

Methods: We assessed immune responses in 50 uninfected individuals who received varying three-dose vaccination combinations (2X AstraZeneca + 1X Moderna, 1X AstraZeneca + 2X Moderna, and 3X Moderna) against wild-type (WT) and Omicron variants at eight months post-vaccination. The serum antibody titers were analyzed by enzyme-linked immunosorbent assays (ELISA), and neutralizing activities were examined by pseudovirus and infectious SARS-CoV-2 neutralization assays. T cell reactivities and their memory phenotypes were determined by flow cytometry.

Results: We found that RBD-specific antibody titers, neutralizing activities, and CD4+ T cell reactivities were reduced against Omicron variants compared to WT. In contrast, CD8+ T cell responses, central memory, effector memory, and CD45RA+ effector memory T cells remained unaffected upon stimulation with the Omicron peptide pool. Notably, CD4+ effector memory T cells even exhibited a higher proportion of reactivity against Omicron variants. Furthermore, participants who received three doses of the Moderna showed a more robust response regarding neutralization and CD8+ T cell reactions than other three-dose vaccination groups.

Conclusion: Reduction of humoral and CD4+ T cell responses against Omicron variants in vaccinees suggested that vaccine effectiveness after eight months may not have sufficient protection against the new emerging variants, which provides valuable information for future vaccination strategies such as receiving BA.4/5 or XBB.1-based bivalent vaccines.

Keywords: Omicron variant; SARS-CoV-2; cellular immune response; neutralizing antibody; vaccination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Vaccines*
COVID-19*
Humans
Memory T Cells
SARS-CoV-2

Substances

COVID-19 Vaccines

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by grants from the Ministry of Science and Technology, Taiwan (MOST 109-2320-B-016-012 and MOST 111-2321-B-016-002), National Science and Technology Council, Taiwan (NSTC 111-2327-B-016-001 and NSTC 112-2321-B-016-002), National Health Research Institutes, Taiwan (NHRI-110A1-MRCO-08212101), Ministry of National Defense Medical Affairs Bureau, Taiwan (MND-MAB-C04-111-016, MND-MAB-C12-112-048 and MND-MAB-D-113160), and Tri-Service General Hospital, Taipei, Taiwan (TSGH-D-110088, TSGH-E-110194 and TSGH-E-112201).