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Study Suggests Attenuated Poultry Virus Vaccine Strains Recombined to Regain Virulence

NEW YORK (GenomeWeb News) – A study online today in Science hints that the live, attenuated viruses used in some vaccines may be able to recombine in their hosts in rare cases, producing viruses that are once again able to cause infection.

The new analysis focused on a bird virus called herpesvirus infectious laryngotracheitis virus, or ILTV, that's known for causing respiratory disease in chickens and other poultry.

Australian researchers used viral genome sequencing and comparative genomics to interrogate new forms of ILTV — belonging to so-called class 8 and class 9 ILTV genotypes — that have been turning up in parts of Australia since 2008, along with three of the vaccines available for preventing these poultry infections in that country.

The virulent class 8 and class 9 viruses emerged not long after a new ILTV vaccine was introduced to Australia, study authors explained.

The Serva vaccine, marketed by Intervet, is based on an attenuated class 7 ILTV originating in Europe that is quite highly diverged from the class 1 viruses found in the two other ILTV vaccines available in the country, called SA2 and A20. Those two vaccines, both from Pfizer, are based on attenuated ILTV strains with Australian origins.

The emergence of previously undetected virulent strains on the heels of the new vaccine's introduction prompted speculation by researchers that the three vaccine strains that were co-circulating in Australia might have recombined with one another to spawn distinct, infectious forms of ILTV.

"The contemporaneous introduction of the Serva vaccine and emergence of new classes of virulent ILTV (classes 8 and 9), together with genetic relatedness of viruses causing recent isolates, led to the hypothesis that the class 8 and 9 viruses may represent sub-populations of viruses within the Serva vaccine or may have arisen after in vivo passages of the Serva vaccine," University of Melbourne veterinary science researcher Joanne Devlin, the study's senior author, and colleagues wrote.

Indeed, when they compared genome sequences for the emergent class 8 and 9 ILTV strains with those from the three attenuated vaccine strains, the investigators found that the new virulent strains shared most of their sequence with the Serva vaccine strain. But the infectious viruses also contained bits of sequence that seem to stem from either SA2 or A20 vaccine strains, they reported.

The team's subsequent analyses supported the notion that these similarities were not a coincidence, but, rather, reflected recombination between strains of ILTV included in the three vaccines. And their targeted analyses of other class 8 and class 9 viruses pointed to similar recombination in other ILTV isolates as well.

This recombination appears to have produced viruses that are more virulent than the attenuated strains from which they nabbed their sequences — a fitness advantage that researchers verified in experiments using pathogen-free chickens infected with the new class 8 and 9 viruses.

"We show that independent recombination events between distinct attenuated vaccine strains resulted in virulent recombinant viruses that became dominant strains responsible for widespread disease in commercial poultry flocks," researchers wrote. "These findings highlight the risks of using multiple different attenuated herpesvirus vaccines, or vectors, in the same populations."