Developing RNA Vaccines to Treat Peanut Hypersensitivity

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Brandi  Johnson-Weaver
Organization: DUKE UNIVERSITY
Fiscal Year: 2024
Award: $200,490
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary/Abstract: Oral immunotherapy with PALFORZIA® is a recently FDA-approved therapy to
treat peanut allergy. This therapy requires daily doses of characterized peanut proteins administered orally to
peanut hypersensitive individuals. A major limitation of the PALFORZIA® therapy is the potential for the onset
of allergic responses and possibly anaphylaxis due to activation of peanut-specific IgE coated mast cells.
Development of hypoallergenic peanut proteins devoid of IgE-mediated granulocyte activation potential may
address the known safety limitations of therapy with PALFORZIA®. The rise of the SARS-CoV-2 pandemic and
rapid production and dissemination of mRNA COVID vaccines has highlighted the benefits of mRNA vaccines
to protect against infectious diseases. The goal of this project is to utilize mRNA vaccine technology to express
peanut proteins that lack and/or disrupt known IgE epitopes to provide a peanut allergen vaccine that does not
induce allergic reactions in hosts hypersensitive to the native allergen. This proposal will utilize the dominant
peanut allergen, Ara h 2, which is recognized by majority of peanut allergic individuals and is sufficient to induce
hypersensitivity in mice, to develop mRNA vaccines that produce native Ara h 2 or mutant Ara h 2 with mutations
in known linear IgE epitopes. The studies described in this proposal will evaluate in vitro protein production, in
vitro IgE-mediated granulocyte activation, in vivo immunogenicity, and in vivo allergic disease activation in hosts
sensitized to the native allergen. The results from this proposal will generate proof-of-concept preliminary data
to support future studies to develop mRNA vaccines expressing multiple peanut proteins to treat peanut-
hypersensitivity in allergic hosts.

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