We proudly announce the Awardee of the Publication of the Month March: Sara HUBER

“Chemical modification of ragweed extract results in an increased safety profile while maintaining immunogenicity”

Sara Huber, Hanneke van der Kleij, Sabrina Wildner, Martin Wolf, Michael Wallner, Heidi Hofer, Claudia Asam, Peter Briza, Fatima Ferreira and Michael Hauser

Abstract: 

Introduction
Along with the rapid spread of ragweed, the corresponding allergy is developing into a significant global health problem. However, until now no commercially available immunotherapy against ragweed exists, which guarantees long-lasting clinical benefits. Now, a commercial subcutaneous chemically modified ragweed‐based immunotherapy product (MRE) was being developed and the immunogenicity and allergenicity comparison with a common ragweed extract (RE) was evaluated .

Methods
Mass spectrometry and dynamic light scattering analyses were used to verify the conservation of the major allergens and if chemical modification was successful. To evaluate allergenicity in humans mediator release experiments using ragweed‐allergic patient sera with high IgE reactivity towards ragweed allergens (confirmed by immunoblot) were performed. Potential differences in IgE binding capacities were recorded by inhibition as well indirect enzyme-linked immunosorbent assays (ELISA). In in vivo mouse models and subsequent indirect ELISA, murine mediator release experiments, IgE-facilitated allergen binding (FAB) and ELISPOT assays showed the allergenic and immunogenic properties of MRE.

Results
Mass spectrometry and dynamic light scattering analyses revealed the conservation of all major allergens in MRE and verified that chemical modification of ragweed extract was successful. Mediator release assays using ragweed‐allergic patientsʼ sera revealed significantly reduced allergenicity for the new therapy candidate. Moreover, indirect and inhibition ELISA using human sera from ragweed-allergic donors showed a statistically significant reduction in IgE-binding in comparison to common ragweed extracts. In in vivo mouse models and indirect ELISA experiments we confirmed that total and specific IgE levels were reduced and at the same time IgG levels were increased. While mediator release experiments in mice revealed similar allergenic potency, IgE‐facilitated allergen binding assays verified that MRE-induced IgG possesses a higher allergen-IgE binding inhibition capacity than common RE-induced IgG. Finally, ELISPOT assays exhibited that MRE induces significantly less major allergy- and inflammatory-triggering cytokines.

Conclusion
In tests with human sera and in in vivo mouse models, we could show that chemical modification of ragweed significantly reduced allergenicity together with unaffected immunogenicity. The significantly reduced IgE-binding capacity of MRE and at the same time high IgG-binding quality, makes it not only a highly valuable candidate to be further tested as vaccine for the treatment of ragweed pollen allergies but also suggests a lower risk profile for allergic side effects during treatment.

The open access article can be found  here.

Reviewed by Hans Brandstetter

CONGRATULATIONS!