If 2021 was the year of mRNA vaccines, could 2022 be the year of epitope-focused vaccines? While that is too soon of a target, scientists at Osaka Prefecture University in Japan did recently lay the groundwork critical to the development of an epitope-focused vaccine against dog allergies.
If the work succeeds through the experimental and clinical phases, the “hypoallergenic vaccine” would not only be a world-first in respect to dogs, but would also open the door to treating a broad range of allergies.
Over the years, scientists have identified seven different dog allergens—named Canis familiaris allergens 1 to 7 (Can f 1-7)—responsible for producing the unusually strong immune response seen in a typical allergic reaction. Now, for the first time, a team led by Takashi Inui has identified the parts of the molecules that make up dog allergies. This information could be used to artificially induce a person’s immune tolerance.
Although there are seven allergens, just one—Can f 1—is responsible for 50 to 75 percent of reactions in people allergic to dogs. But, researchers have yet to identify Can f 1’s IgE epitopes—or the specific parts of the antigens that are recognized by the immune system to stimulate an immune response.
“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,” said Inui, a specialist in allergy research, professor at Osaka Prefecture University and 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, the team was able to determine, for the first time, the structure of the Can f 1 protein as a whole. They found that, at first glance, the protein’s folding pattern is extremely similar to three other Can f allergens. However, the locations of surface electrical charges were different, suggesting a series of “residues” that are good candidates for the IgE epitope.
While there are five classes of antibodies, previous research has shown the IgE isotype, which is only found in mammals, plays a key role in allergies and allergic diseases—regardless of host.
“There is also an IgE epitope that is the puzzle piece that fits the IgE isotype’s paratope,” explains the research team.
There is a long roadmap ahead of the researchers, the first phase being further in vivo work to narrow down the list of residues “candidates.”
Even so, the findings published by Inui and his team in The Federation of European Biochemical Societies Journal lay crucial groundwork for the possibility of a dog allergy vaccine in the near future.