mRNA Initiative

    Penn Vet’s mRNA Research Initiative will fast-track the development of veterinary mRNA-based vaccines and host-directed therapies.

    While mRNA vaccines are efficient at stimulating antibody responses, they are less able to generate enduring skin, lung, and intestinal T cells that are critical for barrier immunity to many pathogens. Leveraging Penn Vet’s immunologic expertise, the first phase of the project will investigate how to generate sustained T cell-mediated immunity in these barrier tissues with mRNA vaccines. Scientific findings from these basic studies will inform our goal of developing veterinary vaccines, including a vaccine for avian influenza in poultry and a vaccine for viral infections in swine.

    Funding for IIZD’s mRNA Initiative was provided by the Penn Institute for RNA Innovation through the support of 2023 Nobel Prize winner Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research at Penn’s Perelman School of Medicine.

    MRNA Cell Closeup

    Investigators: Christopher A. Hunter, Michael J. Hogan, Phillip Scott

    Projects

    Define the Requirements to Generate Protective T cells in Barrier Tissues

    The goals of this project are to understand the requirements for T cell residency in barrier tissues and apply this knowledge to vaccine development. The project will capitalize on our expertise in T cell memory and mRNA technology to improve mRNA vaccines for infections of the skin, lung, and intestinal tract.

    • Natural infections that occur via the skin, lungs, or intestine typically result in a long-lived population of T cells that reside in these tissues. These cells, called resident memory T cells (Trm), provide long-term protection against re-infection precisely where pathogens are most likely to invade.
    • While mRNA vaccines are efficient at generating antibody responses, they are less efficient at generating Trm cells within barrier tissues.
    • The limited ability of of current mRNA vaccines to generate Trm cells remains a major challenge for the development of vaccines against vector-borne infections, and those transmitted orally or through inhalation.
    • A better understanding of the events that lead to the generation of Trm cells during infection has already provided clues to the pathways that can be incorporated into mRNA design to facilitate vaccines that would generate these important cells.

    Develop Vaccines for Veterinary Medicine

    The goals of this project are to develop a pipeline to test mRNA vaccine immunogenicity and efficacy in poultry and swine, while supporting species-agnostic approaches for assessing immune health using transcriptional profiling.

    • mRNA vaccines have had a tremendous impact on human health, but these advances have not yet been applied to the veterinary vaccine field.
    • While the flexible nature of mRNA vaccine design offers a powerful platform for targeting diverse veterinary pathogens, the lack of tools to study species-specific immune responses remains a major obstacle to vaccine development and evaluation.
    • This project will focus on the development of species-specific mRNA vaccines for avian influenza in poultry and swine to provide proof-of-concept studies for this approach.
    • Building on insights from Project I, we will generate and validate species-specific mRNA immune modulators that can be used to augment veterinary mRNA vaccines to generate long-lived protection at barrier surfaces.