Recombined virus from vaccines poses no threat to humans

Two distinct strains of herpesvirus that were used in a live attenuated virus vaccine administered to chickens have been found to have recombined into a new highly virulent strain.

However, this event poses no threat to humans, and the probability of a similar event occurring in human vaccines to produce a new virulent strain of a virus are negligible, say scientists.

Dr Joanne Devlin and Professor Glenn Browning, reporting in Science today, describe how a new virulent virus that has killed a large number of commercially bred chickens originated in a rare recombination event between two live attenuated viruses used in poultry vaccines.

Three different vaccines for herpesvirus are used in Australia, and it appears that two of them – one originating from Australia and one from Europe – have recombined to produce two new strains of infectious laryngotracheitis viruses, types 8 and 9, which have caused mortality rates among commercial chickens of up to 17.6 per cent.

Using whole genome sequencing, the researchers found that the new viruses contained portions of the genomes of both the live attenuated viruses used in the poultry vaccines.

However, live attenuated virus vaccines are relatively uncommon in human vaccines, and where they do exist, such as the Sabin polio vaccine, they are being phased out in favour of inactivated versions, such as the Salk vaccine, said Professor Ian Gust, from the University of Melbourne and the Victorian Biotechnology Advisory Council.

This precludes the possibility of recombination between strains, although it doesn’t remove the possibility of mutations occurring reverting the virus to a virulent form, which is why live attenuated viruses are being phased out, he said.

Furthermore, he stressed that the environmental circumstances in which humans are administered with vaccines are very different to that in the animal health industry. “Administration of herpes vaccines to flocks of chickens is vastly different from the administration of herpes vaccine to humans.”

Where flocks of chickens are kept in high population, high density environments, and given multiple strains of live attenuated virus vaccines, and where virus shedding and transfer are far more likely, the possibility of a recombination event is increased. Such conditions don’t exist among humans who are issued with vaccines.

He pointed out that there has been a live attenuated influenza vaccine in use in the United States in limited numbers since 2003, and there have been no cases of it recombining with wild type influenza.

In fact, he states, the odds of a recombination event occurring and producing a virulent version of a human virus are about the same as the chances of “being kicked to death by a duck,” he said.

However, the finding does have implications for animal health, said co-author Professor Glenn Browning. According to Browning, the use of multiple live attenuated vaccines is common in other species of animal, so this may not turn out to be an isolated case of virus recombination.

“This sort of event could potentially happen in other animal species and with other viruses. So we believe that what we have seen here has potentially got wider implications than just this particular disease in poultry,” he said in a media briefing.

However, the new virus strains should be contained by the existing herpesvirus vaccines, said Dr John Owusu, Australian Pesticides and Veterinary Medicines Authority (APVMA). “The good news is that these new virulent viruses - the existent vaccines are effective against the new viruses.”

The APVMA has already reviewed its procedures in response to the finding, and it planning on establishing a focus group with representatives from the poultry and animal health industries charged with providing advice on regulatory options for use of vaccines.

“We have informed our state and Australian Government regulatory partners and are now working through the implications of these findings with the researchers, vaccine registrants and the poultry industry,” said APVMA Veterinary Medicines Program Manager, Dr Allen Bryce.

“While there are clearly a number of regulatory issues raised by this research, these can be readily accommodated within our current regulatory approach.

“There are a number of short-term measures we are considering, including changes to product labels, which may result in restrictions on the use of two vaccines of different origins in the one animal population.

“We will also assess all live virus vaccines currently registered by the APVMA in regard to the risk of recombination.

“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.”

The paper detailing the recombination event was published in Science today.