There have been many studies that describe the nature and evolution of dog allergies, but there have been few practical studies that use this information to try to completely cure patients with dog allergies by intentionally generating immunological tolerance. But, for the first time, scientists have identified candidates for sections of the molecules that make up dog allergens that could lead to the development of a "dog allergy vaccine."
Their findings were published in the journal of the Federation of European Biochemical Societies.
Being allergic to dogs is a widespread ailment that is spreading over the world. Scientists have identified seven different dog allergens over the years, which are chemicals or molecular structures that attach to an antibody and cause an extremely powerful immune reaction that would otherwise be harmless.
Canis familiaris allergens 1 to 7 are the names given to these seven allergens (Can f 1-7). However, while there are seven, only one, Can f 1, is responsible for the bulk of reactions in those allergic to dogs (50-75 percent). It's found in the tissue of dogs' tongues, salivary glands, and skin.
Can f 1's IgE epitopes — those precise sections of antigens that are recognised by the immune system and trigger or 'determine' an immunological response — have yet to be identified (which is why epitopes are also called antigen determinants). Epitopes are short amino acid sequences that make up a portion of a protein that triggers an immunological response.
Epitopes bind to a specific antigen receptor on the surface of immune system antibodies, B cells, and T cells, similar to how a jigsaw puzzle piece fits into the exact form of another puzzle piece. (A paratope is the portion of the receptor that binds to the epitope).
Antibodies, also known as immunoglobulins, are divided into five categories or isotypes: IgA (immunoglobulin A), IgD, IgE, IgG, and IgM. In allergies and allergic disorders, the IgE isotype (present only in mammals) plays a critical role. There's also an IgE epitope that fits the IgE isotype's paratope like a puzzle piece.
In recent years, a lot of research has gone into producing epitope-focused vaccines, such as this one for dog allergies.
"We hope to be able to give modest doses of these epitopes to the immune system to educate it to cope with them, similar to the premise behind any vaccination," Takashi Inui, an allergy researcher and professor at Osaka Prefecture University, said. "However, we can't accomplish this without first finding the IgE epitope of Can f 1."
As a result, the researchers utilised X-ray crystallography (the analysis of x-ray diffraction through a substance to discover its 'crystal' structure) to determine the structure of the Can f 1 protein as a whole, which was the first time this had ever been done.
They discovered that the protein's folding pattern is strikingly similar to those of three other Can f allergens. The locations of surface electrical charges, on the other hand, were considerably diverse, implying a succession of'residues' that could be potential candidates for the IgE epitope.
More experimental work is needed to narrow down the choices using this basic data, but the findings imply that developing a hypoallergenic vaccination against Can f 1 — a dog-allergy vaccine — is within reach.
The development of a 'hypoallergenic vaccination' using such epitopes would not only be a world first for dog allergies, but it would also be extremely unlikely for any allergic reaction. The principles underpinning the researchers' work could be utilised much more generally against other allergies if their work is used to build a dog allergy vaccine.
Reference:
Masatoshi Nakatsuji, Keisuke Sugiura, Keisuke Suda, Michiko Sakurai, Miki Ubatani, Haruka Muroya, Rina Okubo, Ryo Noguchi, Yoichi Kamata, Yuma Fukutomi, Osamu Ishibashi, Shigenori Nishimura, Takashi Inui. Structure‐based prediction of the IgE epitopes of the major dog allergen Can f 1. The FEBS Journal, 2021; DOI: 10.1111/febs.16252
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