Feline coronavirus: the changing nature of a life-threatening virus

It belongs to the same family as Sars-Cov-2, but affects a different species. The feline enteric coronavirus (FEPV) is a harmless gastrointestinal virus that can mutate into an aggressive form responsible for a lethal systemic disease - feline infectious peritonitis (FIP).

The feline coronavirus, like its human counterpart, consists of an RNA strand and a protein capsule made up of 4 structural proteins:

- Spike (S)

- Envelope (E)

- Membrane (M)

- Nucleocapsid (N)

The virus infects the host by means of the spike protein, which binds to an unknown receptor on the cell surface. The most affected are the cells of the intestine, but the infection is usually asymptomatic or heals spontaneously within a few days. However, the virus can mutate inside the host and turn into a more aggressive version - almost identical to the first, but with a different tropism.

The changing virus

The two biotypes, or pathotypes, of the feline coronavirus are respectively called FEPV (feline enteric coronavirus) and FIPV (feline infectious peritonitis coronavirus). The first is practically harmless, it always remains in the intestine and is asymptomatic or leads to acute episodes of diarrhea and vomiting. The second, on the other hand, infects monocytes and macrophages, which are immune system cells present in the bloodstream and tissues. FIPV, therefore, leaves the intestine and causes a lethal systemic disease, feline infectious peritonitis, characterized by an abdominal effusion that compromises the function of internal organs, in particular the liver, lungs and gastrointestinal system.

Most stray cats (80-100%) and a good portion of domestic cats (25-40%) come into contact with the feline coronavirus at least once in their life. But only a small percentage, 2-6%, develop FIP. The disease, in fact, occurs only in the event that the virus undergoes a mutation within the host organism, which transforms it from the harmless form (FEPV) to the pathogenic one (FIPV).

Researchers have not yet been able to understand what is the mechanism that triggers the transformation of the virus. However, they identified specific mutations in the two forms, in particular in the spike protein. Very few mutations can change the way the protein binds to the receptor and as a result the tropism of the virus also changes. It acquires the ability to infect cells other than enterocytes - particularly monocytes and macrophages.

The challenge for a vaccine

Since early 2020, laboratories around the world have started a global race for the Covid-19 vaccine. In the past, the scientific community had also started experimenting with vaccines against two other coronaviruses, those of Sars and Mers. Despite the efforts, however, to date, there are still no vaccines approved for people against these or other coronaviruses, despite they have been known for almost 60 years.

Even against the feline coronavirus there is still no vaccine. In the past, immunization experiments in cats with live or inactivated viruses have yielded unsatisfactory results. Vaccination even seems to have the side effect of making the cat even more susceptible to the disease. The explanation lies in a mechanism also described for Sars, the "enhancement mediated by antibodies" or ADE (from the English "Antibody-Dependent Enhancement").

ADE occurs when the antibodies stimulated by the vaccine do not neutralize the virus, but provide a secondary gateway into the cells of the immune system. The virus-antibody complexes, in fact, can bind to a receptor expressed on the surface of monocytes and macrophages that recognizes a specific portion of the antibody called Fc. A vaccinated cat could therefore paradoxically be more susceptible to manifesting the symptoms of the disease than an unvaccinated one, since its immune cells would be more likely to be infected.

The road to a safe vaccine is therefore still long and requires a deep understanding of the mechanism of ADE. An alternative could be to design a vaccine that induces  also a strong cellular response by T lymphocytes, which neutralize intracellular pathogens by destroying infected cells. Furthermore, after being activated, they keep the “memory” for longer, which is important for long-term protection.

Our contribution

In Vitares, we contribute personally, together with the companies Takis and Evvivax, to the research for the Covid-19 vaccine. In parallel, our team is developing a project for a genetic vaccine against feline infectious peritonitis. We want to take advantage of our experience with Sars-Cov-2 to design another vaccine against a structurally similar virus. We will use the same technique that has already produced satisfactory results against Sars-Cov-2 in preclinical studies, both as production of anti-spike antibodies and as induction of a cellular response mediated by specific T lymphocytes.

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Erika Salvatori