Projects
PLUG-AND-PLAY MULTI-PATHOGEN VACCINE PLATFORM FOR ANIMAL DISEASE COMPLEXES
Topic: Poxviruses
Summary
Non Technical Summary
Animal disease complexes such as chicken respiratory disease pose a challenge for the development of vaccines due to multi-pathogen etiologies and the need to frequently update the vaccine, as in the case of influenza.We recently developed a novel plug-and-play vaccine technology that allows the rapid and efficient generation of recombinant vaccines based on vaccinia virus, at one genetic locus.We now plan to expand the platform to two genetic loci for the rapid development of multi-antigen, multi-pathogen vaccines that can be rapidly updated as needed.We will develop a multi-pathogen vaccine for respiratory disease complex in chickens expressing protective antigens for infectious bronchitis, infectious bursal disease, and avian influenza. In addition, the vaccine will have a safety feature recently developed in our laboratory for vaccinators and animal handlers. There would be much to gain from a plug-and-play platform that allows rapid generation, testing, and updating of safe multi-pathogen vaccine candidates.
Objectives & Deliverables
Goals / Objectives
Animal disease complexes such as chicken respiratory disease pose a challenge for the development of vaccines due to multi-pathogen etiologies and the need to frequently update the vaccine, as in the case of influenza.Vaccinia virus (VACV) is an excellent live recombinant vaccine vector due to its thermal stability, low cost of production, and ability to elicit strong humoral and cell-mediated immune responses.We recently developed a novel plug-and-play technology that allows the rapid and efficient generation of recombinant VACVs at one genetic locus.We now plan to expand the platform to two genetic loci for the rapid development of a safe multi-pathogen vaccine for respiratory disease complex in chickens expressing protective antigens for infectious bronchitis, infectious bursal disease, and avian influenza.
Challenges
Project Methods
Our plug-and-play platform will be expanded to two genetic loci for the rapid development of multi-antigen, multi-pathogen vaccines that can be rapidly updated as needed, as in the case of influenza vaccines.A new transfer vector targeting the second locus will be generated and cells will be infected with the first-locus VACV and transfected with the transfer vector to generate a new recombinant virus that will serve as the standard plug-and-play parental virus that will allow the quick sequential generation of recombinant VACVs expressing antigens at two loci.The growth kinetics of this VACV will be tested in cell culture to ensure it replicates at wildtype levels.We will then generate a multi-pathogen vaccine for respiratory disease complex in chickens expressing protective antigens for three major respiratory pathogens: infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and avian influenza virus (AIV).A new transfer vector will be generated for expression of the S gene of IBV and the VP2 gene of IBDV at the first loci and the resulting virus will be used for the generation of the final VACV also expressing AI HA at the second loci.The resulting replication-repressible virus will replicate constitutively in the absence of antibiotics, but not in the presence of doxycycline.Finally, we will characterize the multi-pathogen vaccine candidate (expression of S, VP2, and HA proteins will be confirmed by western blot).
Principle Investigator(s)
Planned Completion date: 30/09/2021
Effort: (N/A)
Project Status
COMPLETE
Principal Investigator(s)
National Institute of Food and Agriculture
Researcher Organisations
Recipient Organization UNIV OF CONNECTICUT 438 WHITNEY RD EXTENSION UNIT 1133 STORRS,CT 06269
United Kingdom