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Prophylactic mRNA Vaccination against Allergy Confers Long-Term Memory Responses and Persistent Protection in Mice
E Hattinger1, S Scheiblhofer1, E Roesler1
1Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria.
Abstract:
Recently, mRNA vaccines have been introduced as a safety-optimized alternative to plasmid DNA-based vaccines for protection against allergy. However, it remained unclear whether the short persistence of this vaccine type would limit memory responses and whether the protective immune response type would be maintained during recurrent exposure to allergen. We tested the duration of protective memory responses in mice vaccinated with mRNA encoding the grass pollen allergen Phl p 5 by challenging them with recombinant allergen, 3.5, 6, and 9 months after vaccination. In a second experiment, vaccinated mice were repeatedly challenged monthly with aerosolized allergen over a period of 7 months. Antibody and cytokine responses as well as lung inflammation and airway hyperresponsiveness were assessed. mRNA vaccination induced robust TH1 memory responses for at least 9 months. Vaccination efficiently suppressed TH2 cytokines, IgE responses, and lung eosinophilia. Protection was maintained after repeated exposure to aerosolized allergen and no TH1 associated pathology was observed. Lung function remained improved compared to nonvaccinated controls. Our data clearly indicate that mRNA vaccination against Phl p 5 induces robust, long-lived memory responses, which can be recalled by allergen exposure without side effects. mRNA vaccines fulfill the requirements for safe prophylactic vaccination without the need for booster immunizations.
Insights
Messenger RNA (mRNA) vaccines against grass pollen allergy provide long-lasting protection. These vaccines induce robust immune memory for at least nine months, maintaining protection even with repeated allergen exposure.
Area of Science:
- Immunology
- Vaccinology
Background:
- Messenger RNA (mRNA) vaccines offer a safer alternative to plasmid DNA vaccines for allergy prevention.
- Concerns exist regarding the persistence of mRNA vaccine-induced memory responses and their efficacy during continuous allergen exposure.
Purpose of the Study:
- To evaluate the duration of protective memory responses induced by mRNA vaccination against the grass pollen allergen Phl p 5.
- To assess the maintenance of protective immune responses following repeated allergen challenges.
Main Methods:
- Mice were vaccinated with mRNA encoding Phl p 5 and challenged with recombinant allergen at 3.5, 6, and 9 months post-vaccination.
- A separate group of vaccinated mice underwent monthly aerosolized allergen challenges for 7 months.
- Immune responses (antibodies, cytokines), lung inflammation, and airway hyperresponsiveness were analyzed.
Main Results:
- mRNA vaccination elicited robust T-helper 1 (TH1) memory responses lasting at least 9 months.
- Vaccination effectively suppressed T-helper 2 (TH2) cytokines, immunoglobulin E (IgE) levels, and lung eosinophilia.
- Protection persisted after repeated allergen exposure, with no observed TH1-associated pathology and improved lung function compared to controls.
Conclusions:
- mRNA vaccination against Phl p 5 induces durable, long-lived immune memory responses.
- Allergen re-exposure effectively recalls protective memory without adverse effects.
- mRNA vaccines meet the criteria for safe prophylactic use without requiring booster immunizations.
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