The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated the rapid development and deployment of vaccines worldwide. mRNA-based vaccines against COVID-19 have demonstrated a high degree of efficacy against the original SARSCoV-
2 strain. However, the emergence of several genetic variants of the virus presents significant challenges to worldwide efforts in controlling the pandemic. To date, five dominant variants, namely Alpha, Beta, Gamma, Delta, and Omicron, have caused major epidemic waves of SARS-CoV-2 infections. Understanding the adaptive immune responses induced by COVID-19 vaccines against these variants is crucial for evaluating vaccine effectiveness and informing public health strategies.
COVID-19 mRNA vaccines stimulate robust adaptive immune responses characterized by the production of antibodies targeting the spike (S) protein of SARS-CoV-2 and the generation of memory T cells. In this study, we developed an immunoassay based on SARS-CoV-2 proteins and a live virus microneutralization test (MNT) to measure the production and persistence of vaccine-induced and naturally acquired neutralizing antibodies. Additionally, we employed an activationinduced marker (AIM) assay to analyse the activation of memory T cells against SARS-CoV-2 variants. Immune responses were studied in Finnish healthcare workers.
The results of this study demonstrate that the completion of a two-dose mRNA vaccine regimen leads to consistent and high production of S-specific antibodies across all studied age groups. Vaccinated individuals exhibit the ability to neutralize the SARS-CoV-2 Alpha variant, while neutralization against the Beta and Delta variants is reduced. Furthermore, a majority of vaccinated participants display the presence of SARS-CoV-2 S-specific memory CD4+ and CD8+ T cells, which exhibit cross-recognition of the different SARS-CoV-2 variants. S-specific antibody levels were found to decline within months following vaccination, while T cell responses remained stable for at least six months. These results highlight the durability of memory T cell responses and their role in providing sustained protection against SARS-CoV-2 variants.