# T-cell exhaustion and antibody response in SARS-CoV-2 vaccine recipients

## TL;DR

This study examines how different SARS-CoV-2 vaccination schedules affect T-cell populations and antibody levels, finding that T-cell responses vary but antibody production remains consistent.

## Contribution

The study provides new insights into T-cell exhaustion and subpopulation dynamics across various vaccination regimens.

## Key findings

- Vaccination schedules like 3P+1M+1P reduced CD3+ and CD8+ T cells but increased CD4+ T cells.
- Higher CD8+ T cell percentages correlated with lower CD4+ T cell percentages across all groups.
- No significant differences in anti-spike IgG antibody levels were observed between vaccination platforms.

## Abstract

To evaluate the percentage variations of the total lymphocyte population, T cells (TC), and their subpopulations; to characterize the cellular exhaustion profiles in CD4+ and CD8+ T cells; and to quantify anti-spike IgG antibody levels in individuals who received different vaccination schedules.

We isolated PBMCs (peripheral blood mononuclear cells) from 45 vaccinated and 15 unvaccinated participants to measure TC percentages and MFI (mean fluorescence intensity) by flow cytometry. Additionally, we obtained serum from 42 vaccinated participants, 9 unvaccinated participants, and 20 pre-pandemic controls to measure the concentration of specific IgG antibodies against the SARS-CoV-2 spike protein, respectively.

Vaccination with 3P+1M+1P induced a lower %CD3+ than 3P+1M; a lower %CD8+ than 3P and 3P+1M, but a higher %CD4+ than 3P+1M. All groups, whether vaccinated or not, presented a negative correlation in which a higher %CD8+ corresponded to a lower %CD4+. Cellular exhaustion in CD4+PD1+ of the 3P+1M group was higher than in all CD8+PD1+ of all vaccination platforms including the unvaccinated, except for 3P and the vaccinated or unvaccinated platforms in CD4+PD1+. No significant differences were found in IgG (anti-spike) production across vaccination platforms.

Homologous or heterologous vaccination platforms from three doses onwards do not modify IgG (anti-spike) antibody production; however, they improve CD8+ T cell values, which constitute the most important subpopulation for the antiviral response against SARS-CoV-2.

Evaluar las variaciones porcentuales de la población total de linfocitos, de los linfocitos T (LT) y de sus subpoblaciones; caracterizar los perfiles de agotamiento celular en LT CD4+ y CD8+; y cuantificar los niveles de anticuerpos IgG anti-spike en individuos que recibieron distintos esquemas de vacunación.

Aislamos PBMC (células mononucleares de sangre periférica) de 45 participantes vacunados y 15 no vacunados para medir por citometría de flujo, porcentajes e IFM (intensidad de fluorescencia media) de LT. Además, obtuvimos suero de 42 participantes vacunados, 9 no vacunados y 20 controles prepandemia para medir la concentración de anticuerpos IgG específicos contra la proteína de la espícula del SARS-CoV-2, respectivamente.

La vacunación con 3P+1M+1P indujo menor %CD3+ que 3P+1M; menor %CD8+ que 3P y 3P+1M, pero mayor %CD4+ que 3P+1M. Todos los grupos vacunados o no presentaron una correlación negativa en la que a mayor %CD8+ menor %CD4+. El agotamiento celular en CD4+PD1+ de 3P+1M fue mayor que en todos los CD8+PD1+ de todas las plataformas de vacunación incluyendo los no vacunados, excepto 3P y las plataformas de vacunados o no en CD4+PD1+. No se encontraron diferencias significativas en la producción de IgG (anti-spike) en las plataformas de vacunación.

Las plataformas de vacunación homólogas o heterólogas a partir de tres dosis no modifican la producción de anticuerpos IgG (anti-spike); sin embargo, mejoran los valores de LTCD8+, que constituyen la subpoblación más importante para la respuesta antiviral contra el SARS-CoV-2.