Immunize and disappear-safety-optimized mRNA vaccination with a panel of 29 allergens.
BACKGROUND
The spread of type I allergic diseases has reached epidemic dimensions. The success of therapeutic intervention is limited, and hence prophylactic vaccination is now seriously considered. However, immunization of healthy individuals requires safety standards far beyond those applicable for therapeutic approaches. mRNAs encoding allergen molecules represent an attractive tool for preventive vaccination because of the inherent safety features of this vaccine type.


OBJECTIVE
In the current study we investigated whether mRNA constructs would be capable of protecting against type I allergic reactions in a murine model using the grass pollen allergen Phl p 5 and 28 other major pollen, food, animal, mold, and latex allergens.


METHODS
BALB/c mice were immunized intradermally either with conventional or replicase-based mRNA constructs. Subsequently, animals were sensitized by means of subcutaneous injection of allergen/alum, followed by airway provocation. IgG1/IgG2a/IgE titers were determined by using ELISAs. Allergen-specific functional IgE levels were assessed by using the basophil release assay. Measurement of cytokines in splenocyte cultures and bronchoalveolar lavage fluids were performed by using enzyme-linked immunosorbent spot assays/sandwich ELISAs. Eosinophil and CD8(+) counts in bronchoalveolar lavage specimens were determined by means of flow cytometry. Airway hyperreactivity was assessed with whole-body plethysmography and invasive resistance/dynamic compliance measurement.


RESULTS
mRNA vaccination proved its antiallergic efficacy in terms of IgG subclass distribution, functional IgE suppression, reduction of IL-4 and IL-5 levels, induction of IFN-gamma-producing cells, and reduction of airway hyperreactivity and eosinophil counts in the lung.


CONCLUSIONS
Immunization with mRNA induces T(H)1-biased immune responses similar to those elicited through DNA-based vaccination but additionally offers the advantage of a superior safety profile.
Roesler
Elisabeth
E
Department of Molecular Biology, Christian Doppler Laboratory for Allergy Diagnosis and Therapy, University of Salzburg, Salzburg, Austria.
Weiss
Richard
R
Weinberger
Esther E
EE
Fruehwirth
Angelika
A
Stoecklinger
Angelika
A
Mostböck
Sven
S
Ferreira
Fatima
F
Thalhamer
Josef
J
Scheiblhofer
Sandra
S
D000485:Allergens / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D014612:Vaccines; D007073:Immunoglobulin E