Periodic Reporting for period 1 - Ovavax2 (Accelerating scale up and commercialisation of 100% bacteria free eggs for use in production of vaccines)
Reporting period: 2022-11-01 to 2023-10-31
In excess of 1 bn fertilised specific pathogen free (SPF) chicken eggs are used annually in vaccine manufacture, globally. Eggs play a central role in production of vaccines like flu, yellow fever, smallpox, monkey pox, measles and mumps where a virus is grown in the developing embryo of fertilized eggs. The COVID-19 pandemic has increased an already high global demand for vaccines: while the success of mRNA vaccines may lead to development of future vaccine technology, it is expensive and has a complex supply chain. Traditional vaccine production will continue to play a dominant role in the world’s vaccine strategy, as the methods and infrastructure are well established.
SPF is the term that is used to describe eggs, which are confirmed to be free of various infectious agents e.g. bacteria and viruses. The embryo in the egg is used to grow the virus, the basis of the development and production of vaccines. Globally, there is a world shortage of ‘high grade’ eggs for vaccine manufacture and ongoing supply and contamination issues dictate a need for a superior product. Currently, all eggs used in vaccine manufacture, even those of the highest SPF grade, carry bacteria on the shell and up to 30% of eggs carry bacteria inside the shell. Internalised bacteria cannot be removed without damaging the embryo, rendering it of no use for vaccine production.
Bacterial contamination occurs because the eggshell may absorb contaminating bacteria, from external sources. An eggshell is porous to facilitate gaseous exchange by the growing embryo. The pores of the eggshell are vulnerable to bacterial ingress during laying and for approximately 5 minutes after the egg is laid. Unlike mammals, where the digestive tract is separate from the reproductive tract, in poultry, the reproductive tract merges with the digestive tract, in the cloaca, and there is a single point of exit from the hen for eggs and faeces. This results in the porous egg coming in contact with the chicken’s faeces prior to being laid and consequent contamination of up to 30% of the eggs within the shell occurs. Detection of infectious agents relies on microbiological monitoring but the 4-week lag time required to confirm the presence of infection in the SPF eggs, means that infected eggs will have already been used in vaccine production, causing rejections of batches of vaccines, delays to market and delays to patient vaccinations. It only takes one contaminated egg to destroy a batch of vaccines. The cost of a rejected batch of vaccine can be up to $480,000 with annual losses of $35 million confirmed by one global vaccine manufacturer visited during our extensive market research.
Following 7 years of R&D and solving many intractable problems Ovagen has developed its innovative and disruptive technology to produce the world’ first germ free eggs which will be a game changer for vaccine manufacture. Germ free eggs will transform vaccine production by:
-eliminating bacterial contamination and reducing antimicrobial resistance, a holy grail for vaccines
-increasing the yield of vaccines produced per egg
-increasing quality, security and sustainability
-reducing carbon footprint
-allowing more efficient and cost effective production of vaccines therefore improving access for poorer Nations.
The overall objectives of this project was to radically transform the way egg based vaccines are manufactured globally and to offer an additional solution to the rapid development and manufacture of vaccines in the case of future pandemics.
SPF is the term that is used to describe eggs, which are confirmed to be free of various infectious agents e.g. bacteria and viruses. The embryo in the egg is used to grow the virus, the basis of the development and production of vaccines. Globally, there is a world shortage of ‘high grade’ eggs for vaccine manufacture and ongoing supply and contamination issues dictate a need for a superior product. Currently, all eggs used in vaccine manufacture, even those of the highest SPF grade, carry bacteria on the shell and up to 30% of eggs carry bacteria inside the shell. Internalised bacteria cannot be removed without damaging the embryo, rendering it of no use for vaccine production.
Bacterial contamination occurs because the eggshell may absorb contaminating bacteria, from external sources. An eggshell is porous to facilitate gaseous exchange by the growing embryo. The pores of the eggshell are vulnerable to bacterial ingress during laying and for approximately 5 minutes after the egg is laid. Unlike mammals, where the digestive tract is separate from the reproductive tract, in poultry, the reproductive tract merges with the digestive tract, in the cloaca, and there is a single point of exit from the hen for eggs and faeces. This results in the porous egg coming in contact with the chicken’s faeces prior to being laid and consequent contamination of up to 30% of the eggs within the shell occurs. Detection of infectious agents relies on microbiological monitoring but the 4-week lag time required to confirm the presence of infection in the SPF eggs, means that infected eggs will have already been used in vaccine production, causing rejections of batches of vaccines, delays to market and delays to patient vaccinations. It only takes one contaminated egg to destroy a batch of vaccines. The cost of a rejected batch of vaccine can be up to $480,000 with annual losses of $35 million confirmed by one global vaccine manufacturer visited during our extensive market research.
Following 7 years of R&D and solving many intractable problems Ovagen has developed its innovative and disruptive technology to produce the world’ first germ free eggs which will be a game changer for vaccine manufacture. Germ free eggs will transform vaccine production by:
-eliminating bacterial contamination and reducing antimicrobial resistance, a holy grail for vaccines
-increasing the yield of vaccines produced per egg
-increasing quality, security and sustainability
-reducing carbon footprint
-allowing more efficient and cost effective production of vaccines therefore improving access for poorer Nations.
The overall objectives of this project was to radically transform the way egg based vaccines are manufactured globally and to offer an additional solution to the rapid development and manufacture of vaccines in the case of future pandemics.
Work performed to date on the Project includes:
-Meticulous management of the Project
-Development of marketing collateral, presenting and exhibiting at International meetings/conferences, poster presentation, website and Linkedin information updates
-Execution of four viral yield comparative studies with H1N1 influenza virus, Yellow fever, Newcastles disease virus and COVID-19 virus.
-Signing of Material Transfer Agreements (MTA’s) with a number of global animal and human health vaccine manufacturers a CDMO and a CRO.
-Evaluation of germ free eggs by a number of customers.
-Infrastructure establishment, protocols and test methodologies for in-house Microbiology testing.
-Confirmed contractual agreements with key service providers.
Main achievements include:
-Ovagen germ-free eggs supported replication of human influenza virus H1N1/Victoria with yields up to 2-fold higher than the two main suppliers of SPF eggs.
- Results for Interferon Beta showed a 2 & 3-fold decrease in germ free eggs compared with the two main suppliers of SPF eggs.
-Initial evaluation results received from a global animal health vaccine manufacturer confirmed that Ovagen’s germ free eggs were sterile on arrival at their site and following incubation and that specific tests carried out on the GF eggs identified a significant difference in a positive way in GF vs SPF eggs.
-Meticulous management of the Project
-Development of marketing collateral, presenting and exhibiting at International meetings/conferences, poster presentation, website and Linkedin information updates
-Execution of four viral yield comparative studies with H1N1 influenza virus, Yellow fever, Newcastles disease virus and COVID-19 virus.
-Signing of Material Transfer Agreements (MTA’s) with a number of global animal and human health vaccine manufacturers a CDMO and a CRO.
-Evaluation of germ free eggs by a number of customers.
-Infrastructure establishment, protocols and test methodologies for in-house Microbiology testing.
-Confirmed contractual agreements with key service providers.
Main achievements include:
-Ovagen germ-free eggs supported replication of human influenza virus H1N1/Victoria with yields up to 2-fold higher than the two main suppliers of SPF eggs.
- Results for Interferon Beta showed a 2 & 3-fold decrease in germ free eggs compared with the two main suppliers of SPF eggs.
-Initial evaluation results received from a global animal health vaccine manufacturer confirmed that Ovagen’s germ free eggs were sterile on arrival at their site and following incubation and that specific tests carried out on the GF eggs identified a significant difference in a positive way in GF vs SPF eggs.
In current vaccine manufacturing processes, state of the art/best practice is to use SPF eggs. However, these SPF eggs are not free of bacterial contamination. The key output of this project was the sustainable production of germ free eggs for evaluation by vaccine manufacturers , CDMO’s & CRO’s leading to sales agreements.
This interdisciplinary project will substantially transform how egg based vaccines are produced beyond the current state of the art by fundamentally improving the source material used in vaccine manufacture and replacing it with a superior product resulting in supply chain improvement for vaccine producers. This will radically transform the way egg based vaccines are manufactured globally and ensure rapid access to vaccines to prevent disease particularly in the case of global pandemics.
From studies completed in this project it is proven that low interferon levels in GF eggs increase viral yield per egg for H1N1 influenza virus. Three additional studies on Yellow fever, Newcastles disease virus and COVID-19 have to be conducted as part of the project. Increased viral yield has significant implications for vaccine production i.e. reduced cost of vaccines and enhanced global availability. GF eggs will exponentially increase vaccine yields for manufacturers which will greatly enhance the value of this disruptive technology.
The OvaVax project has successfully advanced the research beyond the current state of the art.
This interdisciplinary project will substantially transform how egg based vaccines are produced beyond the current state of the art by fundamentally improving the source material used in vaccine manufacture and replacing it with a superior product resulting in supply chain improvement for vaccine producers. This will radically transform the way egg based vaccines are manufactured globally and ensure rapid access to vaccines to prevent disease particularly in the case of global pandemics.
From studies completed in this project it is proven that low interferon levels in GF eggs increase viral yield per egg for H1N1 influenza virus. Three additional studies on Yellow fever, Newcastles disease virus and COVID-19 have to be conducted as part of the project. Increased viral yield has significant implications for vaccine production i.e. reduced cost of vaccines and enhanced global availability. GF eggs will exponentially increase vaccine yields for manufacturers which will greatly enhance the value of this disruptive technology.
The OvaVax project has successfully advanced the research beyond the current state of the art.