mRNA Vaccination as a Safe Approach for Specific Protection From Type I Allergy

Authors and Disclosures

Richard Weiss, Sandra Scheiblhofer, Elisabeth Roesle, Esther Weinberger, and Josef Thalhamer*

University of Salzburg, Christian Doppler Laboratory for Allergy Diagnosis & Therapy, Hellbrunnerstrasse 34, 5020 Salzburg, Austria

* Author for correspondence
Tel.: +43 662 8044 5737 Fax: +43 662 8044 5751 josef.thalhamer@sbg.ac.at

Sidebar

Key Issues

• Increasing prevalence of allergy and the resulting socioeconomic burden have emphasized the rationale to develop prophylactic strategies, including allergen vaccines.

• Advances in assessment of genetic predisposition as well as identification of early allergy markers have facilitated selection of appropriate at-risk populations for prophylactic vaccination.

• Several prophylactic vaccination protocols have been established in preclinical models, including peptides and recombinant proteins with or without various adjuvants, bacterial and viral live vectors expressing allergens, and genetic vaccines. For the majority of these approaches the induction of Th1-biased immunity was identified as protective principle.

• Naturally acquired immunity to environmental allergens in many individuals contains a Th1 component (as defined by IFN-γ-secreting T cells). Th1-type memory responses elicited by gene vaccination may therefore closely resemble immunity established under certain natural conditions, such as exposure to microbial agents (hygiene hypothesis).

• mRNA vaccines provide similar protection from allergic sensitization as DNA vaccines, based on Th1 immunity. Induction of a subtle Th1 bias is sufficient as subsequent allergen contact boosts and expands allergen-specific T-cell memory.

• mRNA vaccines provide an excellent safety profile owing to their inability to integrate into the host genome and their short persistence in the body. Owing to these and other facts, mRNA vaccination is not rated as gene therapy by the US FDA and the Paul Ehrlich Institute.

• The safety and efficacy of mRNA vaccines has recently been demonstrated in clinical trials of cancer immunotherapy.

• mRNA vaccines encoding allergens fulfil all necessary requirements for clinical evaluation within the next few years.