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 the project’s goal to develop veterinary vaccines, including a vaccine for avian influenza in poultry, and a vaccine for viral infections in swine.

    Funding for the 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 in 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

    An integrated project to compare the requirements for T cell residency in barrier tissues that will accelerate researchers’ ability to apply this knowledge to vaccines. The project will capitalize on current expertise of memory T cells and mRNA vaccines in 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, resident memory T cells (Trm), that provide protection against re-infection.
    • While mRNA vaccines are efficient at generating antibody responses, they are less efficient at generating the long-lived T cell populations that reside in barrier tissues required for protection against many pathogens.
    • Why mRNA vaccines fail to do this efficiently remains a major barrier to vaccine development for 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 Trm cells

    Develop a Vaccine for Veterinary Medicine

    Develop a pipeline that facilitates the ability to test mRNA vaccine immunogenicity in poultry and swine, while supporting species-agnostic approaches using transcriptional profiling to assess immune health.

    Project II will focus on avian influenza and viral infections of swine and on the development and utilization of tailored species-specific mRNA vaccines to provide proof of concept studies that this approach can augment humoral and cellular responses. The investigation will generate and validate species-specific mRNA immune modulators that can be used to augment and specialize the immune response. It is anticipated that the basic studies supported in Project I will be incorporated into developing novel strategies relevant to veterinary vaccines.

    • The development of mRNA vaccine approaches has had a tremendous impact on human health but has not yet been applied to the veterinary vaccine field.
    • The flexible nature of mRNA vaccine construction makes it a convenient platform to design vaccines for diverse veterinary pathogens, but the ability to study the immune response in different species can limit the ability to assess vaccine efficacy.