Protein structure discovery lays foundation for dog allergy vaccine
Scientists in Japan investigating the possibility of a vaccine for people allergic to dogs have made a significant breakthrough, identifying the crystal structure of a protein at the heart of the majority of dog allergies for the first time. The new understanding of this protein has enabled the researchers to narrow their search for protein components that trigger the immune response characteristic of these allergic reactions, drawing the prospect of a vaccine a step closer.
Scientists have so far identified seven types of allergens that drive allergic reactions to dogs among humans. These molecules bind to antibodies via short amino acid sequences called epitopes, which form part of a protein that induces the immune response. These epitopes bind to receptors on the antibodies called paratopes, like a pair of jigsaw pieces, and one found only in mammals that plays a key role in their allergies is known as the IgE paratope.
Of the seven different types of allergens – named Canis familiaris allergens 1 to 7 (Can f 1-7) – , the one called Can f 1 found in dogs' tongue tissue, salivary glands and skin is behind the majority of allergic reactions among humans, accounting for between 50 and 75 percent of them. As part of the effort to develop a vaccine for dog allergies, the hunt is on to pinpoint the IgE epitope within the Can f 1 protein.
“We want to be able to present small doses of these epitopes to the immune system to train it to deal with them, similar to the principle behind any vaccine,” says Takashi Inui, a specialist in allergy research, professor at Osaka Prefecture University and a lead author of the study. “But we can’t do this without first identifying the Can f 1’s IgE epitope.”
Using X-ray crystallography, Inui and his colleagues were able to identify the crystal structure of the complete Can f 1 protein for the first time. On first impression, the folding pattern of the protein was very similar to three of the other proteins identified previously, but with some differences in the location of surface electrical charges.
This important difference presents a set of "residues" that are strong candidates for the IgE isotope. Though a promising step forward, the scientists note that more work is needed to narrow down these candidates further, but suggest a dog allergy vaccine is within reach. They also say that producing one in this way, by leveraging epitopes, may well offer a blueprint for better defenses against a range of allergies.
The research was published in the journal Federation of European Biochemical Societies.
Source: Osaka Prefecture University