Location: Endemic Poultry Viral Diseases ResearchTitle: Attenuation of NDV LaSota strain by codon pair deoptimization of the HN and F genes is not sufficient for in ovo vaccination
|ELDEMERY, FATMA - ORISE FELLOW|
|OU, CHANGBO - HENAN INSTITUTE OF SCIENCE AND TECHNOLOGY|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/16/2020
Publication Date: N/A
Technical Abstract: In ovo vaccination is an attractive immunization approach for the poultry industry. Currently available Newcastle disease virus (NDV) vaccines cannot be administered in ovo because of the reduced hatchability and embryo mortality. Codon pair deoptimization (CPD) approach has been used for efficient and rapid attenuation of a variety of RNA viruses by targeting the virulence genes through synonymous substitutions to reduce protein production of the target genes with maintained immunogenicity. In this study, we aimed to attenuate the NDV LaSota (LS) strain for in ovo vaccination by CPD of the fusion (F) or/and hemagglutinin-neuraminidase (HN) genes. Three NDV LS recombinants expressing codon deoptimized LS F (rLS/F-d), HN (rLS/HN-d), or both genes (rLS/F+HN-d) were generated by using reverse genetics technology. Biological assays showed that the codon deoptimized viruses maintained similar hemagglutination activity in embryonated eggs as the parental rLS virus. Also, these recombinant viruses retained their growth kinetics similar to the parental rLS virus except rLS/HN-d that showed slightly high titer. The pathogenicity of the rLS/HN-d and rLS/F+HN-d viruses were slightly attenuated with a lower intracerebral pathogenicity index (0.01 and 0.00, respectively) than the rLS and rLS/F-d viruses (0.15 and 0.36 respectively). However, all three codon deoptimized viruses were still lethal to 10-day-old specific-pathogen-free chicken embryos with a mean death time less than 128 hours. These results suggested that the CPD of the surface glycoprotein genes of the LS strain does not sufficiently attenuate the virus for in ovo vaccination, and other virus attenuation approaches are needed to develop a safe in ovo NDV vaccine.