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Presence of SARS-CoV-2-specific T cells before vaccination in the Mexican population
Gabriela Hernandez-Galicia1, Luis Gomez-Morales1,2, Luis Uriel Lopez-Bailon1,2
1Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute, 2508 Instituto Politécnico Nacional Avenue, 07360, Mexico City, Mexico.
Abstract:
The immune response to SARS-CoV-2 has been extensively studied following the pandemic outbreak in 2020; however, the presence of specific T cells against SARS-CoV-2 before vaccination has not been evaluated in Mexico. In this study, we estimated the frequency of T CD4+ and T CD8+ cells that exhibit a specific response to S (spike) and N (nucleocapsid) proteins in a Mexican population. We collected 78 peripheral blood samples from unvaccinated subjects, and the presence of antibodies against spike (RBD) and N protein was determined. Peripheral blood mononuclear cells were isolated and stimulated with a pool of S or N protein peptides (Wuhan-Hu-1 strain). IL-1β, IL-4, IL-6, IL-10, IL-2, IL-8, TNF-α, IFN-γ, and GM-CSF levels were quantified in the supernatant of the activated cells, and the cells were stained to assess the activation and memory phenotypes. Differential activation frequency dependent on serological status was observed in CD4+ cells but not in CD8+ cells. The predominantly activated population was the central memory T CD4+ cells. Only 10% of the population exhibited the same phenotype with respect to the response to nucleocapsid peptides. The cytokine profile differed between the S and N responses. S peptides induced a more proinflammatory response compared with the N peptides. In conclusion, in a Mexican cohort before vaccination, there was a significant response to the S and N SARS-CoV-2 proteins resulting from previous infections with seasonal coronaviruses or previous undetected exposure to SARS-CoV-2.
Insights
Before vaccination, Mexican adults showed T cell responses to SARS-CoV-2 spike and nucleocapsid proteins, indicating prior exposure. Central memory T CD4+ cells were predominantly activated, with distinct cytokine profiles for each protein.
Area of Science:
- Immunology
- Virology
- Epidemiology
Background:
- The immune response to SARS-CoV-2 is crucial, but pre-vaccination T cell specificities in Mexico remained unevaluated.
- Understanding T cell responses is key to characterizing immunity against SARS-CoV-2.
Purpose of the Study:
- To determine the frequency and characteristics of T CD4+ and T CD8+ cells specific to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in an unvaccinated Mexican population.
- To analyze cytokine profiles and T cell activation/memory phenotypes.
Main Methods:
- Collected peripheral blood from 78 unvaccinated Mexican subjects.
- Assessed antibodies against S (RBD) and N proteins.
- Isolated peripheral blood mononuclear cells, stimulated with S or N peptides, and quantified cytokine levels (IL-1β, IL-4, IL-6, IL-10, IL-2, IL-8, TNF-α, IFN-γ, GM-CSF).
- Stained cells to evaluate activation and memory phenotypes.
Main Results:
- Differential activation frequency in CD4+ cells based on serological status, but not in CD8+ cells.
- Central memory T CD4+ cells were the predominantly activated population.
- S peptides induced a more pro-inflammatory cytokine response compared to N peptides.
- Only 10% of the population showed a consistent phenotype for nucleocapsid peptide response.
Conclusions:
- A significant T cell response to SARS-CoV-2 S and N proteins was observed in the unvaccinated Mexican cohort.
- This response likely resulted from prior infections with seasonal coronaviruses or undetected SARS-CoV-2 exposure.
- Findings highlight pre-existing immunity and T cell memory dynamics in the Mexican population prior to widespread vaccination.
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