Development, production and testing of novel glycoconjugate pig vaccines
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: Department of Pathogen Molecular Biology
Abstract
Healthily maintained livestock are essential for economic and societal prosperity. We propose to exploit ground-breaking technology to produce low cost glycoconjugate vaccines to protect against three major pig diseases (porcine pleuropneumonia, Glässer's disease and S. suis-induced meningitis), where current vaccines are unsatisfactory. We have developed technology to generate cloned glycoconjugates in E. coli cells that act as mini factories to produce an inexhaustible and renewal supply of pure vaccine. Due to production costs, conventional chemically synthesised glycoconjugate vaccines have not been used for animals, but have an excellent track record in humans, where over a billion doses have been used. Through the LSHTM business development office and industrial collaborators we will develop, produce and test new vaccines against the three major pig respiratory diseases. A new company, ArcVax, will be spun-out to further develop the technology and commercialise vaccine product.
Publications
Faulds-Pain A
(2019)
The Streptococcos suis sortases SrtB and SrtF are essential for disease in pigs.
in Microbiology (Reading, England)
Kay E
(2024)
Engineering Escherichia coli for increased Und-P availability leads to material improvements in glycan expression technology
in Microbial Cell Factories
Kay EJ
(2022)
Engineering a suite of E. coli strains for enhanced expression of bacterial polysaccharides and glycoconjugate vaccines.
in Microbial cell factories
Majorova D
(2021)
Use of Precision-Cut Tissue Slices as a Translational Model to Study Host-Pathogen Interaction.
in Frontiers in veterinary science
Mauri M
(2021)
Multivalent poultry vaccine development using Protein Glycan Coupling Technology.
in Microbial cell factories
Passmore I
(2020)
Ferric Citrate Regulator FecR Is Translocated across the Bacterial Inner Membrane via a Unique Twin-Arginine Transport-Dependent Mechanism
in Journal of Bacteriology
Passmore IJ
(2019)
Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
in BMC veterinary research
Terra VS
(2022)
PglB function and glycosylation efficiency is temperature dependent when the pgl locus is integrated in the Escherichia coli chromosome.
in Microbial cell factories
| Description | We developed and produced three Actinobacillus pleuropneumoniae toxin vaccine candidates. We cloned and expressed of Strep suis capsular polysaccharides in E. coli as a primary step towards making production of a recombinant Strep suis glycoconjugate vaccine. We developed and produced a App/Strep suis glycoconjugate vaccine candidates. |
| Exploitation Route | We have pig vaccine candidate available for testing. This may still happen through Boehringer Ingelheim, but we are also in discussions with Merck Animal Products. Additionally, pig vaccines are part of the business plan for our spin out company ArkVax, which may provide an additional route to testing vaccines developed and produced in the grant. |
| Sectors | Agriculture Food and Drink Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | The findings from the study have formed the basis for Strep suis pig vaccines. These vaccines are being developed and produced by ArkVax |
| First Year Of Impact | 2023 |
| Sector | Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology |
| Impact Types | Economic |
| Description | Development and application of an Advanced Glycan Production Platform |
| Amount | £447,107 (GBP) |
| Funding ID | BB/W006146/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2022 |
| End | 01/2025 |
| Description | Development of a Universal Group A Streptococcus Glycoconjugate Vaccine |
| Amount | £403,000 (GBP) |
| Funding ID | 221589/Z/20/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2021 |
| End | 01/2023 |
| Description | GlycoCell |
| Amount | £12,300,000 (GBP) |
| Funding ID | BB/Y008472/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2024 |
| End | 02/2029 |
| Description | Institutional Translation Partnership Award |
| Amount | £800,000 (GBP) |
| Funding ID | 214227/Z/18/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2019 |
| End | 03/2023 |
| Description | Reducing the health & economic burden of Campylobacter using a live vaccine |
| Amount | $600,000 (AUD) |
| Funding ID | LP190100114 |
| Organisation | Australian Research Council |
| Sector | Public |
| Country | Australia |
| Start | 09/2021 |
| End | 10/2024 |
| Description | Unravelling the molecular mechanisms of invasive pneumococcal disease |
| Amount | £1,900,000 (GBP) |
| Funding ID | 221803/Z/20/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2021 |
| End | 01/2026 |
| Title | Provision of bank of E coli glycoengineering strains |
| Description | Provision of bank of E coli glycoengineering strains that are available free from the Belgium Co-ordinated Collection of Microorganisms |
| Type Of Material | Biological samples |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The bank of E coli glycoengineering strains that are available free from the Belgium Co-ordinated Collection of Microorganisms were the most requested strains from this major collection in 2023, and we were given an award. |
| URL | https://www.biodiversity.be/5177/#:~:text=BCCM%2FLMG%20is%20a%20bacterial,Contact%3A%20lmg%40UGent.b... |
| Description | Glycoengineering pathways in E. coli |
| Organisation | University of Arkansas Medical Center |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | We have supplied 11 E. coli strains derived from our E. coli GlycoCell project to evaluate for efficiency fro glycosylation and to improve glycol yields based on reshunting UndeCPP pathways. |
| Collaborator Contribution | In collaboration with Professor Matthew Jorgenson, UAMS we are investigating the role of recycling UndeCPP in the efficiency of glycoengineering in E. coli cells |
| Impact | Improved E. coli strains for glycoengineering |
| Start Year | 2020 |
| Description | Hilleman Labs |
| Organisation | MSD Wellcome Trust Hilleman Laboratories |
| Country | India |
| Sector | Charity/Non Profit |
| PI Contribution | Intellectual contribution and vaccine development and production. |
| Collaborator Contribution | Intellectual contribution and vaccine development and production. Vaccine technology Vaccine upscaling and manufacture |
| Impact | Intellectual contribution and vaccine development and production. Vaccine technology Vaccine upscaling and manufacture |
| Start Year | 2020 |
| Description | Merck MSD |
| Organisation | Merck |
| Country | Germany |
| Sector | Private |
| PI Contribution | Collaboration on vaccine development |
| Collaborator Contribution | Intellectual contribution and vaccine development and production |
| Impact | Intellectual contribution and vaccine development and production. Vaccine technology Vaccine upscaling and manufacture |
| Start Year | 2020 |
| Description | huvepharma |
| Organisation | Huvepharma |
| Country | Bulgaria |
| Sector | Private |
| PI Contribution | Intellectual contribution, vaccine development and production. |
| Collaborator Contribution | Intellectual contribution, vaccine development and production. Vaccine technology Vaccine upscaling and manufacture |
| Impact | Intellectual contribution and vaccine development and production. Vaccine technology Vaccine upscaling and manufacture |
| Start Year | 2020 |
| Company Name | ArkVax |
| Description | ArkVax develops vaccines for animals through glycoengineering. |
| Year Established | 2020 |
| Impact | The focus of the company is the development of multicomponent poultry, pig and ruminant vaccines. The business is supported contract research for vaccine candidate from established vet vaccine companies and further funding is currently being sought from a range of investors. |
| Website | https://www.arkvax.com/ |
| Description | 30+ TV interviews (BBC, SKY, Channel 4) on Covid vaccine delivery, production and use |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | 30+ TV interviews (BBC, SKY, Channel 4) on Covid vaccine delivery, production and use. Received 100s of questions from general public many relating to vaccine confidence |
| Year(s) Of Engagement Activity | 2020 |
| Description | 5 international TV interviews (eg BBC News, Swiss and Russian TV) on Covid vaccine delivery, production and use as well as SARS2-CoV epidemiology |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | 5 international TV interviews (eg BBC News, Swiss and Russian TV) on Covid vaccine delivery, production and use. Received dozens of questions from general public many relating to vaccine confidence |
| Year(s) Of Engagement Activity | 2020 |
| Description | 5 invited newspaper articles in Daily Mail TV interviews on Covid vaccine delivery, production and use. |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | 5 invited newspaper articles in Daily Mail TV interviews on Covid vaccine delivery, production and use. Numerous response from general public who have felt reassured about taking Covid vaccine. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Co-Director of Vaccine Centre |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | As Co-Director of LSHTM vaccines Centre have contributed to several vaccines related event for The General Public, Schools and Industry |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.lshtm.ac.uk/research/centres/vaccine-centre |