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Peer-reviewedCC BYClinical Immunology Communications

Comparative analysis of SARS-CoV-2 immune memory in vaccinated and hybrid individuals two years post-exposure

  1. 1Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Medicine, 777 Glades Road, PO Box 3091, Boca Raton, FL, 33431, USA
  2. 2Corresponding author.

Abstract

Assessing vaccine effectiveness and longevity through measurements of vaccine-induced serum antibodies, as well as memory B and T cells in circulating blood years after vaccination, serves as an indicator of protection and durability. Here, we build upon studies by assessing serum levels of SARS-CoV-2 spike (S) protein–specific immunoglobulins, as well as the status of S protein–specific immune memory in both vaccinated individuals and those with hybrid immunity. We aimed to determine whether the patterns of immune memory reported up to six months post-vaccination in the literature still remains two years after vaccine exposure. Both vaccination and hybrid immunity elicited durable and robust antigen-specific T- and B-cell responses, with memory subsets remaining detectable for up to two years post-exposure. Individuals with hybrid immunity showed greater expansion of central, effector memory, and effector T-cell subsets and produced more IFN-γ per cell upon antigenic stimulation, indicating superior functional quality of effector cells. Our B-cell analyses revealed that hybrid-immune individuals had a higher frequency of S-specific B cells that, upon expansion, differentiated more rapidly into plasmablasts and plasma cells, resulting in increased numbers of these subsets. In contrast, vaccinated individuals exhibited higher S1-specific IgG levels in both culture supernatants and serum. Given the limited number of independent donors, these findings provide an exploratory characterization of long-term vaccine- and hybrid-immunity responses in these populations. Taken together, our findings indicate that approximately two years after exposure, hybrid-immune individuals maintain robust cellular immune responses, while vaccinated individuals retain higher S1-specific IgG antibody responses.

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BibTeX
@article{lee2026comparative,
  title = {{Comparative analysis of SARS-CoV-2 immune memory in vaccinated and hybrid individuals two years post-exposure}},
  author = {Czdari Lee and Imtisal Imran and Sara Thomas and Mahyar Nouri-Shirazi},
  journal = {Clinical Immunology Communications},
  year = {2026},
  month = oct,
  doi = {10.1016/j.clicom.2026.100144},
  url = {https://doi.org/10.1016/j.clicom.2026.100144},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Comparative analysis of SARS-CoV-2 immune memory in vaccinated and hybrid individuals two years post-exposure
AU  - Czdari Lee
AU  - Imtisal Imran
AU  - Sara Thomas
AU  - Mahyar Nouri-Shirazi
PY  - 2026
DA  - 2026/10/30
JO  - Clinical Immunology Communications
DO  - 10.1016/j.clicom.2026.100144
UR  - https://doi.org/10.1016/j.clicom.2026.100144
AB  - Assessing vaccine effectiveness and longevity through measurements of vaccine-induced serum antibodies, as well as memory B and T cells in circulating blood years after vaccination, serves as an indicator of protection and durability. Here, we build upon studies by assessing serum levels of SARS-CoV-2 spike (S) protein–specific immunoglobulins, as well as the status of S protein–specific immune memory in both vaccinated individuals and those with hybrid immunity. We aimed to determine whether the patterns of immune memory reported up to six months post-vaccination in the literature still remains two years after vaccine exposure. Both vaccination and hybrid immunity elicited durable and robust antigen-specific T- and B-cell responses, with memory subsets remaining detectable for up to two years post-exposure. Individuals with hybrid immunity showed greater expansion of central, effector memory, and effector T-cell subsets and produced more IFN-γ per cell upon antigenic stimulation, indicating superior functional quality of effector cells. Our B-cell analyses revealed that hybrid-immune individuals had a higher frequency of S-specific B cells that, upon expansion, differentiated more rapidly into plasmablasts and plasma cells, resulting in increased numbers of these subsets. In contrast, vaccinated individuals exhibited higher S1-specific IgG levels in both culture supernatants and serum. Given the limited number of independent donors, these findings provide an exploratory characterization of long-term vaccine- and hybrid-immunity responses in these populations. Taken together, our findings indicate that approximately two years after exposure, hybrid-immune individuals maintain robust cellular immune responses, while vaccinated individuals retain higher S1-specific IgG antibody responses.
SN  - 2772-6134
ER  -