Comparative analysis of SARS-CoV-2 immune memory in vaccinated and hybrid individuals two years post-exposure
Year: 2026
Type: article
Study design: Observational Study
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.
Institution: Florida Atlantic University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,860
Funder: Florida Atlantic University
OpenAlex ID: W7223172882
