Periodic Reporting for period 1 - BoVLP-BVD (Development of Tagged (DIVA), Virus-Like-Particle polyantigenic Vaccine against Bovine Viral Diarrhea virus (BVDc))
Periodo di rendicontazione: 2017-06-01 al 2017-11-30
"The need to reduce the use of antibiotics to fight diseases in livestock animals is widely accepted, and translates in increased environmental, social and legal pressure. Cost-effective vaccination as an alternative to antibiotic treatment has become the focus of most of the industry and European regulators. In bovine cattle breeding, one of the diseases with most economical and environmental impact is Bovine Viral Diarrhoea (BVD). This disease is the most common viral disease of cattle in Europe. The clinical symptoms are difficult to identify because they are very variable or they can also go undetected (subclinical disease). Despite this, the BVD causes very high economic losses in all countries with developed bovine cattle breeding, making it a real ""time bomb."" For example, Animal Health Ireland estimates that the annual cost of BVD for the Irish hut is 102 million Euros.
The control and prevention of bovine viral diarrhea virus (BVDV) infections has substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. The current unmet need is a broad spectrum, cost-effective and safe BVDV vaccine that avoids the potential risks related to attenuated vaccines (the current gold standard) and allows the discrimination of immunized animals from infected animals to facilitate integrated, “campaign-driven” approaches to fight the disease.
Aquilon’s vaccine, based on proprietary Virus-Like Particle technology, will be a recombinant, non-live vaccine, polyantigenic (covering type 1 and type 2 infections), with tagging attributes (DIVA, Differentiation of Vaccinated from Infected Animals). In this context, the main objective of this phase I project was to confirm the technical, commercial and regulatory feasibility for a novel non-live, poly-antigenic, tagged, recombinant vaccine against the Bovine Viral Diarrhoea virus (BVDV).
Results from the economic risk-benefit analysis combining prospective regulatory costs and timelines, manufacturing scale up and prospective cost of goods, technical feasibility and commercial interest indicate that the project represents a good investment opportunity satisfying a relevant veterinarian unmet need with a strong impact in the society beyond the economics of the livestock animal industry.
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The control and prevention of bovine viral diarrhea virus (BVDV) infections has substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. The current unmet need is a broad spectrum, cost-effective and safe BVDV vaccine that avoids the potential risks related to attenuated vaccines (the current gold standard) and allows the discrimination of immunized animals from infected animals to facilitate integrated, “campaign-driven” approaches to fight the disease.
Aquilon’s vaccine, based on proprietary Virus-Like Particle technology, will be a recombinant, non-live vaccine, polyantigenic (covering type 1 and type 2 infections), with tagging attributes (DIVA, Differentiation of Vaccinated from Infected Animals). In this context, the main objective of this phase I project was to confirm the technical, commercial and regulatory feasibility for a novel non-live, poly-antigenic, tagged, recombinant vaccine against the Bovine Viral Diarrhoea virus (BVDV).
Results from the economic risk-benefit analysis combining prospective regulatory costs and timelines, manufacturing scale up and prospective cost of goods, technical feasibility and commercial interest indicate that the project represents a good investment opportunity satisfying a relevant veterinarian unmet need with a strong impact in the society beyond the economics of the livestock animal industry.
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The work performed was directed to explore the economic feasibility of a novel vaccine against BVDV with prospective attributes based on the characteristics of the Virus-Like Particle (VLP) technology to be used for its development. The exploration focused in three aspects:
1. Commercial feasibility: is there an unmet need with a significant market and does the prospected Target Product Profile of the Aquilon’s vaccine satisfies it?
2. Technical feasibility: is it possible to obtain a cost-effective, industrial vaccine using Aquilon’s VLP technology, and
3. Regulatory feasibility: is the regulatory road map compatible with the timelines and costs required for making the project a reasonable investment opportunity, taking into account the technological and commercial risks ahead?
1. Commercial feasibility: an in depth analysis of the current competitive enviromment and market size was performed, confirming that there is a need for a broad spectrum stand-alone vaccine that allow the discrimination between infected and treated animals, thus facilitating the implementation of contention policies. The market size in the EU is estimated to be in the 600M€ range, with a conservative estimate of 30 to 50M€ sales for the Aquilon’s vaccine.
2. Technical feasibility: the main challenge and necessary condition to the project to be technically feasible was to define the antigens to be used to combine in the Virus-Like Particles in order to obtain testable vaccine prototypes. We screened more than 25 different peptides derived from the main BVDV antigens, using sera from infected animals to see which antigens were naturally reactive (the assumption was, if the infected animals had produced antibodies against a given peptide, this peptide will be immunogenic once expressed in the surface of the particles of the vaccine). The results are very promising, having found three highly reactive peptides that will be included in multiple copies in the VLPs in order to obtain testable and defined poly-antigenic vaccine prototypes. The finding of these peptides will allow to file for new composition of matter patents, thus increasing the commercial appeal of the project.
3. Regulatory feasibility: a regulatory roadmap was elaborated taking into account the attributes of the vaccine and the disease (recombinant, non-live, poly-antigenic, tagged, manufactured in yeast). The time-lines and costs of the regulatory program (including manufacturing scale up) are thus available and can be integrated into a business plan projection in order to define the overall economic feasibility of the project
Dissemination: At this stage, due to confidentiality reasons, the dissemination efforts are put in describing in the corporate web page the project goals and prospective product profile without entering into technical aspects. Once we achieve the first prototype proof of concept and filed the patents we will elaborate non-confidential and confidential dossiers in order to share with prospective partners. The discovery of immunoreactive antigenic determinants in the BVD virus is a relevant scientific contribution that will be integrated in scientific communications once the work is completed and the patents are filed.
1. Commercial feasibility: is there an unmet need with a significant market and does the prospected Target Product Profile of the Aquilon’s vaccine satisfies it?
2. Technical feasibility: is it possible to obtain a cost-effective, industrial vaccine using Aquilon’s VLP technology, and
3. Regulatory feasibility: is the regulatory road map compatible with the timelines and costs required for making the project a reasonable investment opportunity, taking into account the technological and commercial risks ahead?
1. Commercial feasibility: an in depth analysis of the current competitive enviromment and market size was performed, confirming that there is a need for a broad spectrum stand-alone vaccine that allow the discrimination between infected and treated animals, thus facilitating the implementation of contention policies. The market size in the EU is estimated to be in the 600M€ range, with a conservative estimate of 30 to 50M€ sales for the Aquilon’s vaccine.
2. Technical feasibility: the main challenge and necessary condition to the project to be technically feasible was to define the antigens to be used to combine in the Virus-Like Particles in order to obtain testable vaccine prototypes. We screened more than 25 different peptides derived from the main BVDV antigens, using sera from infected animals to see which antigens were naturally reactive (the assumption was, if the infected animals had produced antibodies against a given peptide, this peptide will be immunogenic once expressed in the surface of the particles of the vaccine). The results are very promising, having found three highly reactive peptides that will be included in multiple copies in the VLPs in order to obtain testable and defined poly-antigenic vaccine prototypes. The finding of these peptides will allow to file for new composition of matter patents, thus increasing the commercial appeal of the project.
3. Regulatory feasibility: a regulatory roadmap was elaborated taking into account the attributes of the vaccine and the disease (recombinant, non-live, poly-antigenic, tagged, manufactured in yeast). The time-lines and costs of the regulatory program (including manufacturing scale up) are thus available and can be integrated into a business plan projection in order to define the overall economic feasibility of the project
Dissemination: At this stage, due to confidentiality reasons, the dissemination efforts are put in describing in the corporate web page the project goals and prospective product profile without entering into technical aspects. Once we achieve the first prototype proof of concept and filed the patents we will elaborate non-confidential and confidential dossiers in order to share with prospective partners. The discovery of immunoreactive antigenic determinants in the BVD virus is a relevant scientific contribution that will be integrated in scientific communications once the work is completed and the patents are filed.
The feasibility of the project has been extensively explored thanks to the phase I instrument and the conclusion is that the investment required to develop the vaccine is acceptable given the commercial and social interest of the unmet veterinarian need addressed. The discovery of novel, surprisingly high immune-reactive peptides during the technical screening allows to file for new patent applications and brings new relevant knowledge to the BVD field. The continuation of the project is granted, with a prospected time to market of 6 years and sales in the 30 to 50M€ range. The impact of the vaccine in countries where the bovine hut is relevant can be estimated in hundreds of million euros, and most important, the project will bring to the market a tool to manage a very relevant disease without using antibiotics and with an integrated, programmed approach aiming to eradication based on the capability to discriminate vaccinated from non-vaccinated animals.