Title: Experimental risk assessment of recombinant Newcastle disease virus vaccines Authors
Submitted to: American Association of Avian Pathologists
Publication Type: Abstract Only
Publication Acceptance Date: December 30, 2012
Publication Date: July 20, 2013
Citation: Miller, P.J., Diel, D.G., Hamal, K., Afonso, C.L., Suarez, D.L. 2013. Experimental risk assessment of recombinant Newcastle disease virus vaccines [abstract]. American Association of Avian Pathologists. CDROM. Interpretive Summary: Typically live vaccines for Newcastle disease are “wild type” viruses that were recovered from infected birds. Now, scientists and vaccine companies are able to manipulate the genetic structures of Newcastle disease viruses (NDV) in the lab to create one specific for their market needs. These sort of live recombinant NDV (rNDV) vaccines are used in Mexico and soon to be used in China. We are testing in a laboratory setting the stability and safety of these types of viruses. Our objectives are to: 1) determine the risk of rNDV vaccines made less virulent to revert to their highly pathogenic type; and 2) determine the abilityof rNDV vaccines to infect and transmit in pigeons and sparrows. We also compared the rNDV to wild type NDV strains. While infected 14-day-old embryonating chicken eggs (ECSs) with rNDV and wild type NDV had high mortality, the sequence of the fusion protein cleavage site (which is an indicator of virulence) did not change under these experimental conditions. When rNDV were inoculated in pigeons and sparrows we observed that these viruses are able to infect this species and also spread between infected and non-infected contact birds. All birds that were inoculated with these viruses excreted virus in oral and/or cloacal secretions and at least one of four contact birds excreted virus for two or more days. So far, results suggest rNDV are stable and are not at a higher risk of mutation than wild type NDV.
Technical Abstract: Recombinant Newcastle disease viruses (NDV) used as live vaccines were assessed for: 1) the potential for recombinant NDV-vectored vaccines (rNDV) containing the Avian Influenza virus (AIV) H5 gene to recombine with low pathogenicity H5, H6 and H9 AIV strains, and originate a virus with increased virulence; 2) the risk of rNDV vaccines, containing an attenuated fusion (F) protein cleavage site, to revert back to a virulent virus phenotype; and 3) to assess the ability of rNDV vaccines to infect and spread in non-target species. Co-infection of 14-day-old embryonating chicken eggs (ECE) with rNDV-LaSota/AI-H5 and LPAI strains, rA/whooper/Mongolia/2005 (H5), A/duck/Penn/97 (H6), or A/ruddy_turnstone/NJ/02 (H9) resulted in the death of 90% of the embryos within 72 hours (hr) post-inoculation (PI). Infection of 14-day-old ECEs with wild type NDV strains [LaSota and Australia] or with rNDV strains [LaSota (rLaSota) or ZJ1 (rZJ1*Lento)] (900 eggs/virus) resulted in the death of 65 (7.2%), 10 (1.1%), 23 (2.5%), and 6 (0.6%) embryos, respectively, within 72 hr PI. Sequencing of the F gene cleavage site, under our experimental conditions, revealed all rNDV are stable without reversion to a virulent phenotype. Experiments to assess the ability of rNDV to infect and spread in pigeons and sparrows have shown that rLaSota, and rLaSota/AIV-H5 are able to infect and spread in these species. All virus-inoculated pigeons shed the virus in oral and/or cloacal secretions and at least one out of four contact birds shed the virus for two or more days. These findings suggest that our system is suitable to assess the risk associated with recombinant NDV vaccines.