Thesis: Group A Streptococcal Peptides Expressed in HBsAg-S VLPs as a Vaccine Candidate
Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements...
Transcript of Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements...
![Page 1: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/1.jpg)
Future of vaccine development and commercialization
Holly S. Sellers, MS, PhDPoultry Diagnostic and Research Center
College of Veterinary Medicine
University of Georgia, Athens, GA
![Page 2: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/2.jpg)
Expectations of vaccines…
• Prevent and reduce disease and production losses
• Increase resistance to infection
• Reduce virus replication and shedding• Reduce transmission to susceptible
birds• Reduce environmental contamination
• Cannot• Eradicate disease• Sterilizing immunity
![Page 3: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/3.jpg)
Important considerations of vaccination programs• Type of production system
• Level of protection needed
• Presence of regional diseases• Severity
• Cost
• Post-vaccinal reactions versus production loss
• Is vaccine available?https://thepoultrysite.com/articles/spray-vaccination-of-dayold-chicks-at-the-hatchery
![Page 4: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/4.jpg)
Viral vaccines at a glance…
• Conventional• Killed whole virus
• Live attenuated virus
• Recombinant• Reverse genetics
• Vectored
• DNA
• Subunit
![Page 5: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/5.jpg)
Conventional live vaccines
• Attenuation of pathogenic virus• SPF embryo or cell culture passages
until reduced pathogenicity
• Time consuming
• Types of live vaccines • Tissue culture origin (TCO)
• Chicken embryo origin (CEO)
• Mass administration • Hatchery – in ovo, spray, subcutaneous
• On farm – spray, water, eye drop
![Page 6: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/6.jpg)
Inactivated/killed vaccines
• Killed/adjuvant vaccines
• Enhance immune response without infection• Water-in-oil (WO)
• Oil-in-water (OW)
• Water-in-oil-in water (WOW)
• Aluminum salts
![Page 7: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/7.jpg)
Recombinant vaccines
• Replicating virus (Vector) + gene/s that code for protective immunogenic proteins (Field virus)• Fowlpox (FP)
• Cellular immunity
• Herpesvirus of turkeys (HVT) –serotype 3 Marek’s disease virus• Persistent, systemic infection• Stimulates humoral and cell mediated
immunity
• Newcastle disease virus (NDV)• Mucosal immunity• Interference with maternal antibodies
HVTFPND
Field virus Vector Virus
Inserted gene
Expressed protein
Clone geneof interest
=IMMUNE RESPONSE AGAINST PROTECTIVE ANTIGEN, NOT WHOLE FIELD VIRUS
Slide courtesy of Dr. Darrell Kapczynski – USDA/NPRC
![Page 8: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/8.jpg)
Recombinant vaccines
• Success of recombinant vaccines depends on• Safety
• Efficacious
• Cost effectiveness
• Mass administration
![Page 9: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/9.jpg)
Current commercial recombinant viral vaccines for poultry
Company Virus Vector
Boehringer-Ingelheim Trovac NDV FP
CEVA Vectormune FP ND FP
CEVA Vectormune FP LT FP
CEVA Vectormune FP LT AE FP
Boehringer-Ingelheim VAXXITEK HVT+IBD HVT
Boehringer-Ingelheim NEWXXITEK HVT+ND HVT
Boehringer-Ingelheim PREVEXXION RN Chimera
CEVA Vectormune HVT ND & SB1 HVT
Merck Animal Health Innovax MDV HVT
*No commercial endorsement implied
![Page 10: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/10.jpg)
Company Virus Vector
Merck Animal Health Innovax ND SB HVT
CEVA Vectormune HVT+IBD HVT
CEVA Vectormune HVT+IBD & SB1 HVT
CEVA Vectormune ND HVT
Merck Animal Health Innovax ND ILT HVT
Merck Animal Health Innovax LT SB HVT
Merck Animal Health Innovax LT HVT
Merck Animal Health Innovax ND IBD HVT
CEVA Ultifend ND IBD HVT
Boehringer-Ingelheim VAXXITEK HVT+IBD+ND HVT
*No commercial endorsement implied
![Page 11: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/11.jpg)
Recombinant vaccines for Avian Influenza Virus (AIV)• Many exist worldwide in areas where AIV
is endemic• In U.S. conditional licenses were issued for
several recombinant AIV vaccines during/after the 2014-2015 high path AI outbreak• Zoetis - Reverse engineered/killed
• US H5 – modified cleavage site• Boehringer-Ingelheim – Fowlpox/H5• Alphavirus RNA particle - GyrFalcon/U.S./2014• CEVA – HVT-H5 – Swan/Hungary/2006 • AgriLabs - DNA vaccine H5
• Platforms to accommodate changes in H5 to match outbreaks
![Page 12: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/12.jpg)
Technologies for current and future vaccine development
![Page 13: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/13.jpg)
Recombinant vaccinesReverse genetics• Construction of avian influenza
reassortant vaccine viruses
• Reverse engineered (RE) vaccines in China for AIV H5N1• RE-1 A/goose/Guangdong/1/1996
• RE-2
• RE-3 A/bar-headed goose/Qinghai/3/2005
• RE-4 A/chicken/Shanxi/2/2006
• RE-5 A/duck/Anhui/1/2006
• RE-6 A/duck /Guangdong/1332/2010
• HA cleavage site altered from high path to low path
![Page 14: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/14.jpg)
Deletion mutants
• ILTV with gG deletion
• Live virus
• Protection against clinical signs of disease following challenge with virulent ILTV
• Stimulates systemic, mucosal and cellular immune responses
• Less pathogenic than live ILTV whole virus vaccines
![Page 15: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/15.jpg)
Virus like particles (VLPs)
https://www.creative-biolabs.com/virus-like-particles-vlps-for-vaccine-development.html
Pushko, et. al., Virology, 2017
![Page 16: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/16.jpg)
DNA vaccines
• Antigen-encoding gene is cloned into a non-replicating expression plasmid
• Host cells take up plasmid and express the antigen
• Easy to manipulate plasmid/switch genes
• Stable
• Humoral and cellular immunity
• DIVA compatible
Lee, L.Y.Y., et al, Front Imm, 2018
![Page 17: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/17.jpg)
RNA particle vaccines
• Alphavirus -based replicon particles used as expression system • Accurate production of native proteins• Replication-defective nature • Only capable of a single infection cycle
• RPs not shed from vaccinated animals -> cannot spread to unvaccinated animals
• Platform used for custom vaccines for swine influenza [Sequivity – Merck]
• A conditional license for avian influenza H5
https://www.alphavax.com/alphavaccine-platform.html
![Page 18: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/18.jpg)
“Omics” approach to vaccines
• Genome derived/epitope driven vaccines
https://epivax.com/immunogenicity-assessment/ivax-web-based-vaccine-design
![Page 19: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/19.jpg)
Microarray Scan
(Double Spots)
Data Analysis
Antigen Sequence
Overlapping Peptides
Peptide Microarray
Secondary Antibody
Target Antibody
Post vaccine
Post challenge
Epitope = Consensus Motif
Epitope mapping
![Page 20: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/20.jpg)
Research priorities for vaccine development
![Page 21: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/21.jpg)
Research needs
• Research priorities were assembled by the American Association of Avian Pathologists (AAAP) research priorities committee
• Annual survey of veterinarians in• Association of Veterinarians in Broiler Production (AVBP)
• Association of Veterinarians in Egg Production (AVEP)
• Association of Veterinarians in Turkey Production (AVTP)
• Association of Poultry Primary Breeder Veterinarians (APPBV).
• Purpose to communicate applied research needs of industry to researchers and funding agencies
![Page 22: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/22.jpg)
Vaccines topped list of priorities across sectors • Infectious bronchitis virus (IBV)
• Improved vaccines, enhanced safety characteristics
• Cross-protective
• Reovirus• Develop efficacious and innovative live and inactivated vaccines
• Provide protection against current and emerging strains
• Autogenous vaccines (custom made vaccines)• Improve speed and efficiency of production
• Develop more efficient methodologies to select viral and bacterial isolates
![Page 23: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/23.jpg)
Working closely with industry• Isolate, identify and characterize viruses from clinical cases
• Track emergence of new viruses
• Evaluate protection/cross protection afforded by current commercial vaccines
• Maintain database with diagnostic results for tracking viruses over time and location
• Isolates for autogenous vaccines • Avian reoviruses, Infectious bursal disease viruses, Adenoviruses
• Attenuate new viruses that emerge or continue to cause disease in the field• Infectious bronchitis virus (GA08)• Takes time
![Page 24: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/24.jpg)
Commercialization through partnerships with Universities• Pathways for new vaccine
development• R&D• Acquisition of company with
technology/vaccines • Acquisition of vaccine/technology
from a University
• Universities with competitive research programs have Innovation teams/departments that facilitate technology/intellectual property for licensing • @ UGA -> Innovation Gateway
![Page 25: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/25.jpg)
In the next 5-10 years• Adjuvant technologies will be incorporated into vaccines – cytokines,
nanoparticles, toll like receptor ligands
• Continued development of recombinant platforms
• Vaccine advancements
• License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon
• Conventional vaccines will continue to serve the poultry industry in an important role
• Vaccine licensure: Time from application to field use will decrease.
![Page 26: Future of vaccine development and commercialization · 17.11.2019 · •Vaccine advancements •License of nucleic acid vaccines, VLPs, subunit and synthetic are on the horizon](https://reader033.fdocuments.us/reader033/viewer/2022050216/5f61d45f9742ea68b93425ad/html5/thumbnails/26.jpg)
Thanks for your attention!