Recombination of poultry vaccines: questions and answers
On 13 July 2012, the international journal Science (external site) published a paper detailing Australian research showing that certain live attenuated virus vaccines can recombine to form new and more virulent strains of the field virus.
The vaccines in question are registered for use in the Australian market place to help control a common poultry disease called infectious laryngotracheitis—or ILT for short.
What is ILT?
Infectious laryngotracheitis (ILT) is an acute respiratory disease in chickens. It is caused by the ILT virus, which belongs to the herpesvirus family. It results in mild to severe respiratory disease in poultry worldwide. Economic losses result from mortality and decreased egg production.
The ILT virus does not cause disease in humans.
What does the Science study reveal?
The Science reports work by the Asia-Pacific Centre for Animal Health at The University of Melbourne that shows that two different vaccine viruses used to control ILT have recombined (crossed) to form more virulent forms of the virus.
How do vaccines work?
Vaccines are used to protect humans and animals from disease by stimulating an immune response—a specific controlled response to a disease-causing organism—which results in ongoing, long-term protection against the disease through the formation of antibodies.
Vaccines are grouped according to whether they contain living or killed organisms. Killed organisms are less likely to provide as strong an immune response as those containing living organisms. Those vaccines that contain living organisms are called live virus vaccines. These viruses are prepared using live functional viruses which have reduced ability to cause disease (attenuated) but which retain their ability to induce immunity.
Live attenuated viruses have been used in vaccines worldwide for many years. The ILT vaccines approved for use in Australia contain live attenuated viruses.
How many ILT virus vaccines are registered in Australia?
There are three ILT virus vaccines registered in Australia: two of these, the A20 and SA2 vaccines are closely-related vaccines of Australian origin and have been available for use in Australia for more than 50 years; in 2006, the European-origin Serva vaccine strain was approved for use for the first time. The SA2 and A20 vaccines have a genetic makeup that is distinctly different from the Serva strain—they are therefore classified as different "genotypes" (or sub-types).
Do viruses often recombine?
Recombination is a natural process that can occur when two viruses infect the same cell at the same time. While recombination has been recognised as a potential risk associated with live virus vaccines for many years, the likelihood of it happening in virus vaccines like ILT in the field has been thought to be negligible.
The Australian Science Media Centre (external site) has prepared an infographic (external site) showing how recombination might have occurred in chickens from the two different types of ILT virus vaccines.
How did the ILT vaccine viruses combine?
The recombination is believed to have occurred when poultry flocks were simultaneously exposed to two different vaccine virus strains.
How was recombination identified this time?
Recombination was identified because of the involvement of the Asia-Pacific Centre for Animal Health at The University of Melbourne and its use of full genome sequencing technology. Genetic recombination was one of many scenarios considered by the research team to explain the ILT disease outbreaks that were occurring—all other possible causes were eventually ruled out by the research.
What does the recombination mean long term?
It means that there are two known additional strains of the ILT virus circulating in the environment that have the potential to cause mortality in chickens. Flocks can be vaccinated against these new viruses using the existing registered vaccines.
Importantly, the demonstration of this recombination "in the field" rather than under experimental laboratory conditions, means that what was once a hypothetical possibility, is now much more likely under the right field conditions, not only for ILT vaccines, but potentially for live virus vaccines used in other animal species.
Can vaccine viruses recombine in other animals?
The University of Melbourne research shows that if the same population of animals is simultaneously exposed to live vaccines of two different origins, then recombination is a possibility. There are likely to be many other factors that contribute to the risk of recombination occurring, such as animal husbandry, timing and management of vaccination regimes, and on-farm biosecurity practices.
Who approves veterinary vaccines in Australia?
The APVMA assesses and approves all veterinary medicines—including vaccines—for use and sale in Australia. Vaccines, or vaccine components, that are sourced from overseas must go through an additional import permit process managed by the Department of Agriculture, Fisheries and Forestry. Once approved for entry into the country, the APVMA assesses the vaccine to ensure it can be used safely and authorises its use subject to various conditions.
When did the APVMA first learn of this instance of recombination?
The APVMA was alerted to the research by an APVMA Science Fellow, Professor Glenn Browning, Director of the Asia-Pacific Centre for Animal Health at The University of Melbourne in early 2012. After examining outbreaks of ILT in different poultry flocks in New South Wales and Victoria from 2007 the team from the Asia-Pacific Centre for Animal Health concluded that recombination had occurred. Professor Browning provided the APVMA with a briefing and advised that the team had submitted a formal scientific paper documenting the research for publication in Science.
What did the APVMA do after being briefed by Professor Browning?
In April 2012 (after the research paper had been accepted by Science) the APVMA invited Professor Browning to brief NSW and Victorian co-ordinators of the National Registration Scheme for Agricultural and Veterinary Chemicals. NSW and Victoria were selected for consultation as these are the states where outbreaks of ILT have occurred since 2007 that have been shown to be attributable to novel strains of ILT virus resulting from recombination between the vaccine strains.
In May 2012, again at the invitation of the APVMA, Professor Glenn Browning presented the team's findings to officials from the Australian Government Department of Health and Ageing, the Department of Agriculture, Fisheries and Forestry and the Department of Sustainability, Environment, Water, Population and Communities.
In July 2012, the APVMA met with chicken industry representatives and vaccine manufacturers to discuss key issues associated with the supply and use of ILT virus vaccines in Australia.
What is the APVMA doing?
Although the Science paper clearly raises a number of regulatory issues and provides an objective basis for regulatory action the science does not suggest that a major change to our current regulatory approach is required.
The APVMA has commissioned work to identify other instances where there is a potential risk of vaccine strains recombining to form virulent field viruses.
We have also formed an inter-agency reference group to share information, exchange knowledge and expertise, and act as the conduit for providing feedback to their respective organisations.
A number of short-term measures are being considered, including changes to product labels, which may result in restrictions on the use of two vaccines of different origins in the one animal population.
Longer-term measures may include changes to the regulatory process for new vaccine applications to address the potential for recombination in our scientific risk assessments.
Other action could include registrants voluntarily adding warning statements or restrictions on use or the APVMA conducting a full chemical review leading to variation in condition of use or cancellation of registration if risks cannot be mitigated.
The APVMA will also work with the poultry industry and vaccine manufacturers to identify voluntary activities that might raise awareness of the issues.
In the long term, the APVMA is likely to develop new data requirements for all new vaccine registrations that would include a comparison of the virulence of overseas parent strains and endemic strains of virus (presently, there is no such requirement).
Applicants may also be requested to provide an explanation for why recombination between the intended vaccine strain and endemic strains does not pose a risk. The APVMA will also develop an appropriate risk assessment methodology for assessing this information.
Should the new vaccine be removed from the market to prevent further problems?
The scientific evidence does not justify this action. The new virus strains that arose by recombination are now circulating freely; they have become the dominant viruses circulating in the field. Each of the currently available vaccines is still effective in preventing ILT outbreaks. There are sometimes supply problems with vaccines, and having alternative vaccines available helps to ensure flocks are protected. Removal of one or more vaccines from the market would not eliminate the new viruses, and could result in many more birds dying as a result of inadequate vaccination.
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