Infectious bronchitis control: Understanding why it’s so difficult
By Mark W. Jackwood, PhD
JR Glisson Professor of Avian Medicine
University of Georgia
Poultry producers around the world are all too familiar with infectious bronchitis, a highly contagious viral disease of chickens caused by a coronavirus. Although traditionally thought of as an upper-respiratory disease, some infectious bronchitis virus (IBV) strains can infect the kidneys and cause nephritis or lead to decreased egg production and quality if they infect the oviducts of hens.
This isn’t the only way IBV causes losses, however. The virus also predisposes broilers to secondary bacterial infections such as Escherichia coli, resulting in poor performance, condemnations at processing and mortality. Controlling IBV, therefore, not only prevents the disease but it decreases secondary bacterial infections, which significantly reduces performance problems as well as the use of antibiotics in poultry.
The best strategy for IBV control is the use of live, attenuated vaccines in broilers coupled with a combination of live followed by killed vaccines in breeders and layers. However — as many producers also know — complete protection is difficult to establish because different IBV types don’t cross protect.
If there were a finite number of IBV types, we could simply make vaccines against each one. But new types of IBV continue to emerge without warning, making it difficult to stay ahead of the disease. The emergence of new IBV types boils down to the ability of the virus to rapidly change when it replicates. Those new IBV types can avoid the immune response and infect and replicate, even in previously immunized birds.
How replication leads to IBV changes
IBV has a single-stranded RNA genome (set of genes). By nature, RNA viruses change much more rapidly than DNA viruses. In fact, RNA viruses change so fast we can actually measure their molecular evolution after only a few passages in chickens.
Changes in the viral RNA occur because the virus-encoded protein (RNA polymerase) responsible for copying the virus RNA has a very poor proofreading mechanism. Consequently, when the RNA polymerase makes a mistake, it has trouble going back and fixing it.
In addition, the viral RNA polymerase is prone to making mistakes. Those mistakes are called mutations, and when they occur in key places in the genome of the virus, they can result in the emergence of a new virus type. As long as the virus is free to replicate and transmit to naïve or partially protected birds, mutations will accumulate. The mutations that provide a fitness advantage will persist and eventually result in the emergence of a new IBV type that’s capable of infecting and causing disease.
Genetic drift versus recombination
There’s an important structural protein found in all coronaviruses, including IBV. It’s called the spike or S glycoprotein. The S glycoprotein forms club-shaped projections on the surface of virus particles (Figure 1). The S glycoprotein is used to identify the IBV type. It’s responsible for attachment to host cells and for inducing the development of a protective immune response in the chicken. By and large, new IBV types emerge through mutations in the S glycoprotein that accumulate over time, which is referred to as genetic drift.
Coronaviruses can also undergo recombination. That’s where two parent viruses contribute parts of their genome to create a new chimeric virus. In simplest terms, a chimeric IBV is a new virus that has a mixture of genes from two or more different IBV types. The genetic shift that occurs from recombination can happen rapidly, but it rarely results in a new IBV type capable of causing disease because of the mechanisms involved.
IB- control options
It’s well established that IBVs with completely different spike proteins do not cross protect and that homologous (similar) attenuated, live vaccines provide the best protection. As noted before, it’s impossible to develop homologous attenuated, live vaccines for all the different IBV types found in chickens.
Cross protection is sometimes possible, but it generally decreases with declining similarity between S glycoproteins. In other words, the less similarity there is between a vaccine and the IBV type circulating in the field, the less likely there is to be protection.
Conversely, there are several factors that likely contribute to cross protection. One is the similarity of conserved regions in the spike proteins between different IBV types and the ability of antibodies binding to those conserved regions to neutralize the virus. Another likely factor is the strength of the immune response; some vaccines elicit a stronger immune response than others, but that usually accompanies a strong vaccine reaction. Other factors are the number of vaccinations given, which strengthens the immune response, and the combination of different IBV vaccine types, which contributes to a broader antibody response.
Cross protection cannot be predicted with confidence and must be tested in chickens. Once the type of IBV circulating in the field is identified, we can draw from past experience to design an appropriate vaccination strategy. If the field virus is new and, consequently, there is no past experience to draw upon, then the field virus S glycoprotein sequence can be used to identify vaccines with a similar spike sequence for testing in chickens. The “new” vaccine strategy must then be tested in the laboratory using specific-pathogen-free (SPF) chickens, or it can be “field” tested by adopting the new vaccine strategy for the next flock of birds.
Laboratory testing is the best alternative since variables that can confuse the outcome of the test are kept to a minimum. Although not difficult, it does require the appropriate facilities, time, money and expertise. Basically, SPF chicks are vaccinated according to the new strategy to be adopted, held for a period of time (usually 4 or 5 weeks) in isolation units then challenged with the field virus. The birds are evaluated for protection 5 days after challenge by examining them for clinical signs and lesions typical of IBV and by attempting to reisolate the challenge virus. It’s important to include control groups to verify the validity of the experiment. Ideally, this testing would be conducted each time a new variant virus is identified or when the current vaccination strategy is not working.
Developing a vaccination strategy with either homologous vaccine types or with a combination of heterologous vaccine types given multiple times is important for IBV control because it can reduce field-virus replication to below transmission levels, which prevents or at least slows the emergence of new IBV types that may be capable of causing disease.
Infectious bronchitis is a highly contagious upper-respiratory disease in chickens caused by the avian coronavirus IBV. The disease is difficult to control with vaccination because different types of the virus, which do not cross protect, continue to emerge in commercial poultry.
Because IBV is an RNA virus, it can change very rapidly when it replicates. Mutations that occur in the S glycoprotein gene can alter the makeup of that protein on the surface of the virus resulting in the emergence of new IBV types.
Using a vaccine that has an S glycoprotein identical to the pathogenic virus causing disease in the field is the best approach for controlling IBV. But since we don’t have vaccines against all of the circulating IBV types, a combination of different IBV types in the same vaccination multiple times can sometimes provide enough cross protection to prevent transmission and replication, thus diminishing the chances of new IBV types emerging.
Editor’s note: The opinions and recommendations presented in this article belong to the author and are not necessarily shared by the editors of Poultry Health Today or Zoetis.
Posted on January 3, 2019