"Characterization of adaptive immune dynamics of BNT162b2 immunization by single cell sequencing".
SARS-CoV-2; BNT162b2; scRNA-seq
The severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic. The adoption of public policies, particularly mass vaccination, were essential in fighting and mitigating the negative impacts of the pandemic on public health. In this context, vaccine platforms based on messenger RNA (mRNA) were revolutionary, demonstrating advantages in terms of speed of production and efficacy. Despite the availability of data characterizing innate and adaptive immune responses to different vaccines against COVID-19, molecular dynamics and processes in mRNA vaccines still require further investigation, which, in turn, could help improve vaccine formulations against possible emerging coronaviruses. In this work, using public single cell RNA sequencing (scRNA-seq) data from individuals vaccinated by BNT162b2, it was possible to characterize adaptive immunity dynamics induced, longitudinally, by the immunizer with a complete vaccination schedule. The present work demonstrated particular cellular dynamics after immunization, associated with a profound but transient specific T lymphopenia, with expansion of B cell populations, such as plasmablasts and memory B cells. Differential gene expression analysis showed expression of cellular activation, proliferation and cytotoxicity markers in B and T lymphocytes, in addition to progressive expression of INF-I over the post-vaccination time periods. Notwithstanding, gene ontology analysis highlighted terms that corroborate to the transcriptional profile findings. Furthermore, the determination of B and T subpopulations enabled trajectory inference analyses, deepening findings of post-vaccination cellular dynamics and, finally, cell-cell communication analyzes could establish interactional and signaling patterns between cell groupings indicating non-exclusive, however crucial, participation of pathways such as FTL3, MIF and BAFF/APRIL promoted by the immunization. The results obtained in the present work highlighted cellular and molecular mechanisms that propels the development of more efficient, effective and safer mRNA vaccines against future pandemics associated with coronaviruses and other emerging infectious diseases.