Antigen persistence following mRNA vaccination and the immune consequence of lymph node stromal cell delivery

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B182
Abstract ID: 4718

Presenting Author:
Robert F Belfon , PhD Candidate at Univ. of Colorado Anschutz Med. Campus

Abstract:

mRNA vaccines have demonstrated their usefulness on a global scale in recent years. They elicit potent humoral and cell mediated responses, but the specific mechanisms by which these responses are produced still require investigation. Our lab described a process termed antigen archiving, in which antigen is retained within lymph node stromal cell (LNSC) subsets following viral infection and subunit vaccination to bolster/prolong memory CD8 T cell responses. Whether mRNA vaccines utilize this mechanism to promote immunity has yet to be determined. Data suggest mRNA-derived antigen persists within LNSC of C57/BL6 mice for at least 3 wks following subcutaneous or intramuscular delivery. We investigate the immune consequence of this prolonged antigen retention using ionizable lipid nanoparticles (LNP) to deliver mRNA constructs encoding the model antigen ovalbumin as well as a fluorescent siinfekl-GFP to monitor antigen-specific T-cell responses and localization of antigen within murine lymph nodes (LNs). We identified LNP formulations facilitating differential uptake/translation within LNSC which also demonstrated robust antigen-specific CD8 T cell responses and persistence of antigen presentation within LNs for at least 3 wks in vivo. We plan to interrogate the immune consequences of enhanced stromal cell targeting and subsequent antigen retention following mRNA vaccination. A better understanding of mRNA and protein delivery and retention will inform future vaccine design.