Progress 09/01/18 to 01/25/21
Outputs
Target Audience:Scientists and business professionals employed at international vaccine and diagnostics companies were the target audience of this project. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training and professional development for the Larad technical staff and project director Linda Michel in the area of molecular expression of proteins in the baculovirus system. The knowledge gained from conducting this project is being applied to other Larad products that are still in development. Additionally, Linda Michel attended the Larta Commercialization Training Workshop in Washington, DC in November of 2018 and the American Association of Avian Pathologists Annual Meeting in Washington, DC in August of 2019. How have the results been disseminated to communities of interest?For proprietary reasons and for future patenting of the intellectual property, none of the results from this project have been publicly disclosed. We have confidentiality agreements with Ceva Animal Health and BioChek BV and have disclosed some but not all of these results to those companies. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
The Phase II project had four technical objectives to achieve the goal of creating a CAV-VLP. The specific objectives and work completed toward each of these objectives is summarized below. Objective 1: Generate a "Category IV Summary Information Format" (SIF) and "Risk Assessment" for the CAV-VLPs and expression system for submission to the CVB. The SIF has been written and will be submitted to the CVB with the Outline of Production. Objective 2: Develop a relative potency ELISA test that is acceptable to the CVB for evaluation of the CAV-VLP final product. Total proteins from baculovirus producing CAV-VLPs or CAV-VP3 were prepared for use in ELISA. We observed some non-specific binding that is leading to higher than desired background signal in the ELISA. Therefore, we fused a maltose binding protein to CAV VP2 and VP3. The resulting fusion proteins were purified over amylose resin and this process has reduced the ELISA background. These antigens are currently under evaluation by BioChek and Indical Biosciences for use in a diagnostic ELISA kit. Objective 3: Conduct inactivation kinetics, efficacy, potency, and field safety studies required by the CVB for product licensure. We conducted two in vivo experiments. After a single priming dose the CAV-VLP vaccine was partially protective. While these preliminary studies were promising, in our Phase III study we will test the efficacy of a higher dose and adding a booster vaccination with adjuvant. Objective 4: Generate an "Outline of Production" for submission to CVB that will be used to regulate the CAV-VLP bulk product production, final formulation, fill, quality assurance and distribution of the product. Larad's option agreement with CEVA provides for the CAV-VLP vaccine to be produced at their USDA approved facilities. CEVA is using procedures developed as part of this Phase II grant to develop the Outline of Production for CVB.
Publications
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Progress 09/01/19 to 08/31/20
Outputs
Target Audience:Scientists and business professionals employed at international vaccine and diagnostics companies were the target audience during this period. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has provided training and professional development for the Larad technical staff and project director in the area of molecular expression of proteins in the baculovirus system. The knowledge gained from conducting this project is being applied to other Larad products that are still in development. How have the results been disseminated to communities of interest?For proprietary reasons and for future patenting of the intellectual property, none of the results from this project have been publicly disclosed. We have confidentiality agreements with Ceva Animal Health and BioChek BV and have disclosed some but not all of these results to those companies. What do you plan to do during the next reporting period to accomplish the goals?We plan to complete histopathology, qPCR and data analysis for the CAV vaccination-challenge study samples. We continue to work with Ceva on an outline of production.
Impacts
What was accomplished under these goals?
Objective 1: Generate a "Category IV Summary Information Format" (SIF) and "Risk Assessment" for the CAV-VLPs and expression system for submission to the CVB. The SIF has been written but has not yet been submitted to the CVB. Objective 2: Develop a relative potency ELISA test that is acceptable to the CVB for evaluation of the CAV-VLP final product. Total proteins from baculovirus producing CAV-VLPs or CAV-VP3 were prepared for use in ELISA. We observed some non-specific binding that is leading to higher than desired background signal in the ELISA. We therefore constructed r-baculoviruses containing CAV VP2 or VP3 fused to maltose-binding-protein. These fusion proteins increase expression and can be partially purified over amylose agarose resin and used as ELISA antigens. We have found that this dramatically decreases ELISA background. Objective 3: Conduct inactivation kinetics, efficacy, potency and field safety studies required by the CVB for product licensure. Vaccination-challenge experiments in chickens have recently been completed using two different concentrations of our CAV-VLP. We are in the process of sample and data analysis. Objective 4: Generate an "Outline of Production" for submission to CVB that will be used to regulate the CAV-VLP bulk product production, final formulation, fill, quality assurance and distribution of the product. This objective is in the process of being completed with cooperation from CEVA.
Publications
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Progress 09/01/18 to 08/31/19
Outputs
Target Audience:Scientists and business professionals employed at international vaccine companies were the target audience during this period. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Linda Michel attended the Commercialization Training Workshop in Washington, DC in November of 2018 and the American Association of Avian Pathologists Annual Meeting in Washington, DC in August of 2019. How have the results been disseminated to communities of interest?Since all the work conducted on this project is designed to produce VLP vaccines, the results are only provided to interested parties after a Confidential Disclosure Agreement (CDA) is executed. Larad, Inc. has CDA's with four vaccine companies and has provided proprietary information to those companies on our vaccine production processes. What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, Larad, Inc. scientists will continue with the next steps for each of the objectives. Specifically we will submit a SIF and OOP to the CVB (objectives 1 and 4), validate our relative potency ELISA (objective 2) and complete inactivation kinetics, efficacy, potency, and field safety studies required by the CVB for product licensure (objective 4).
Impacts
What was accomplished under these goals?
Objective 1: Generate a "Category IV Summary Information Format" (SIF) and "Risk Assessment" for the CAV-VLPs and expression system for submission to the CVB. The SIF has been written but has not yet been submitted to the CVB. Objective 2: Develop a relative potency ELISA test that is acceptable to the CVB for evaluation of the CAV-VLP final product. Total proteins from baculovirus producing CAV-VLPs were prepared for use in the ELISA. We observed some non-specific binding that was leading to a higher than desired background signal in the ELISA. Therefore, we purified the antigen and reduced the ELISA background to acceptable levels. Objective 3: Conduct inactivation kinetics, efficacy, potency, and field safety studies required by the CVB for product licensure. A preliminary efficacy and potency test was performed by vaccinating birds with a heat inactivated CAV-VLP preparation. No lesions or reactions at the vaccination site were observed. A CAV ELISA performed with serum collected during the study revealed the presence of anti-CAV antibodies in the vaccinated birds. Objective 4: Generate an "Outline of Production" for submission to CVB that will be used to regulate the CAV-VLP bulk product production, final formulation, fill, quality assurance and distribution of the product. This objective is in the process of being completed with cooperation from a vaccine company partner.
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