Leveraging lipid nanoparticle mRNA platform for combined adjuvant delivery

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B975
Abstract ID: 7948

Presenting Author:
Michael Harbell , graduate student at Univ. of Colorado Anschutz Med. Campus

Abstract:

Lipid-particle encapsulated mRNA (LNP-mRNA) vaccines have undoubtedly demonstrated their ability to lessen and prevent disease during the COVID-19 pandemic. However, the capacity for LNP-mRNA vaccines to generate T cell responses, in particular CD8s, is limited. In contrast, a combined adjuvant consisting of anti-CD40 antibody and type I IFN induces a magnitude of cellular immunity, in both mice and non-human primates, on par with that observed in response to infectious challenge. Clinical implementation of this combined vaccination would be simplified by utilizing LNP-mRNA formulations, avoiding the complications of manufacturing and purification of both adjuvant and antigen. Mice inoculated with Ova-LNP and escalating amounts of heavy and light chain mRNA-LNP for the agonistic CD40 antibody FGK4.5, generated a substantially enhanced response compared to that of OVA-LNP alone. Enhanced responses were also observed after administration of mRNA-LNP encoding heavy and light chains specific for the CTLA4 blocking antibody 9H10. Thus, both agonistic and antagonistic therapeutic antibodies can be expressed in vivo as active molecules, able to effect immunological function. The use of LNP-encapsulated antibody-encoding mRNAs may be an ideal means by which vaccination and checkpoint blockade be achieved in a clinical setting. Exploration of both the utility and mechanisms underlying the success of encapsulated antibody mRNA delivery are the subject of ongoing experimentation.