COVID-19 vaccination: lessons to be learned from veterinary coronavirus vaccines

Bovine coronavirus (BCoV)

BCoV belongs to the genus Betacoronavirus, family Coronaviridae, and it was first described in the United States by Mebus et al in 1972. It is associated with neonatal calf diarrhoea and newborn calves are affected by acute diarrhoea with extensive destruction of absorptive intestinal epithelium leading to dehydration and potentially death.

Successful vaccines have been developed based on inactivated and adjuvanted whole virus technologies (eg Rotavec Corona and Lactovac). These vaccines also incorporate antigens from bovine rotavirus and E. coli. They are licensed for the active immunisation of pregnant cows and heifers to raise protective virus neutralising antibodies. The antibodies produced are fed to calves during the first few weeks of life to reduce disease through passive immunity. This protection will persist as long as the calves are fed stored colostrum or allowed to naturally suckle from their mother. Thus, it is clear in this case that the anti-coronavirus neutralising antibodies which are predominately directed at the virus spike proteins can provide protective immunity through passive transfer and ongoing mucosal administration.

Avian infectious bronchitis virus (IBV)

IBV belongs to the genus Gammacoronavirus, family Coronaviridae, and the respiratory disease was first described by Schalk and Hawn in the US in 1931. Subsequently the viral cause was established by Beach and Schalm in 1936. It is a major pathogen of chickens and causes an acute respiratory disease followed by a reduction in both the quantity and quality of egg production.

Live vaccines, which can be attenuated through passage in embryonated chicken eggs, have been developed using a variety of virus strains with differing pathologies (M41, H120, H52, Ma5, 4/91, D388, etc). The various antigenic types do not generally induce significant cross-protection and this makes it extremely important that the appropriate vaccine(s) is chosen for protection of a particular flock of birds.

The vaccines are administered topically through drinking water, aerosol spray or oculo-nasally, and examples of marketed products include the trade names Nobilis and Poulvac. They are initially given to one- to 14-day-old chicks, and birds are commonly revaccinated approximately two weeks after the initial vaccination. It is interesting to note that revaccination with a different coronavirus strain can induce broader protection. The vaccines can be used in breeders and layers to prevent egg production losses, as well as to pass protective maternal antibodies to progeny. Thus, in this case antibodies that appear to be directed against the coronavirus spike protein are also critical in providing protective immunity, although a role for cell mediated immunity cannot be ruled out. It has been shown that major histocompatibility complex restricted cytotoxic T-lymphocytes (CTL) are responsible for early control of IBV infection. The kinetics of viral load observed in the lungs and kidneys correlates with the level of IBV-specific CTL activity of effector cells prepared from spleens of infected chicks. Furthermore, the adoptive transfer of immune T cells to chicks prior to infection has shown that IBV primed CD8+ve T lymphocytes can protect chicks from acute infection. In addition, the correlation between IBV vaccine type and protection is imperfect, and selection of the most appropriate vaccine, or combination of vaccines, may require experimental assessment in vivo for an optimal immunization schedule to be developed.

Feline infectious peritonitis virus (FIPV)

FIPV belongs to the genus Alphacoronavirus, family Coronaviridae. It was first described by Holzworth in 1963, and it wasn’t until 1970 that Ward identified a virus in the US, similar to known coronaviruses, as the pathogen causing the disease. It is related to feline enteric coronavirus (FECV), and early signs of FIP are usually vague with a fluctuating fever, lethargy and inappetence being common. In most cases of FIP, once clinical signs have begun to develop they tend to get progressively worse over time, and generally result in deteriorating disease to the point that euthanasia is usually required. Two main forms of the disease are known as ‘wet’ or ‘effusive’ disease, and ‘dry’ or ‘non-effusive’ disease. The spike (S) protein of FIPV has been identified as critical for efficient macrophage infection and a chimeric virus in which the S protein of FECV replaces that of FIPV displays a reduced ability to infect macrophages. Furthermore, an imbalance between the T-cell and B-cell immune responses has been suggested as one reason for the inability of cats to resist FIPV infection.

Many approaches to develop an FIP vaccine have been attempted in the past and one of the most cautionary results comes from a recombinant vaccinia virus-encoded FIPV S protein approach, which resulted in early death in cats. In addition, a membrane and nucleocapsid protein DNA vaccine failed to protect cats against FIP, indicating that the surface S protein is likely to be important, and this study also demonstrated that IL-12 may produce adverse effects when used as a cytokine adjuvant.

Data presented by Scott et al (1992) indicated that the ability of an FIP vaccine to protect cats against experimental challenge is dependent upon the strain and particularly the dose of challenge virus. Low dose exposure resulted in protection of more than 50 percent of vaccinated cats, while higher dose exposure resulted in virtually no protection and induced accelerated FIP in many cases as a result of antibody-dependent enhancement (ADE). A further study identified the sites on FIP spike protein which mediate the ADE using monoclonal antibodies.

The only currently licensed vaccine against FIP, called FELOCELL, is an attenuated, temperature-sensitive strain of FIP virus propagated on an established feline cell line. This is administered by intranasal (IN) vaccination of healthy cats to 16 weeks of age or older, as an aid in preventing FIP disease.