COVID-19 vaccine type controls stromal reprogramming in draining lymph nodes

Area of Science:

• Immunology
• Vaccinology
• Cell Biology

Background:

• Lymph node (LN) stromal cells regulate immune responses.
• The impact of SARS-CoV-2 vaccines on LN stromal cells is unknown.

Purpose of the Study:

• To investigate how different SARS-CoV-2 vaccines affect LN stromal cells.
• To understand the early immune events within draining LNs after vaccination.

Main Methods:

• Immunization of mice with mRNA and adenovirus SARS-CoV-2 vaccines.
• Multimodal bioimaging and single-cell transcriptomics of draining LNs.
• Functional assays assessing antigen handling and immune cell migration.

Main Results:

• mRNA and adenovirus vaccines transfected specific LN stromal cell subsets (lymphatic endothelial cells, fibroblastic reticular cells).
• Early, vaccine-specific S protein production occurred in draining LNs.
• Vaccine administration induced transcriptomic changes in stromal cells, altering antigen scavenging, chemokine gradients, and eosinophil migration.

Conclusions:

• Distinct SARS-CoV-2 vaccine formulations differentially prime LN stromal cells.
• Stromal cell reprogramming influences early immune microenvironment modulation before migratory dendritic cell arrival.