Progress 09/01/19 to 08/31/21

Outputs
Target Audience:The target audience for year 1 of this project was internal stakeholders and externally the USDA Center for Veterinary Biologics. Year 1 was focused on preliminary tasks necessary for licensure of the vaccine with USDA. We have been engaged with the CVB during this period and are completing tasks outlined in our project that are necessary for vaccine licensure. Year two of this award continued the work with internal stakeholders andexternal workwith the USDA CVB on the licensure process for this vaccine. Year two saw the approval of our masterseed viruses by the CVB, allowing for the licensing path to continue. Once the product nears commercial launch, conversations with veterinarians and producers will beginto educate them on the product. Changes/Problems:No significant changes were made to this project and all five objectives have been completed. Although our duration of immunity study, objective 4, did not last the full 6 months due to reasons outlined in the final report, the experiment was still completed and valueable information was obtained. The approval of our masterseed viruses was an important milestone in the licensing process, as there were modifications and additional testing requested by CVB and was subject to their timelines. We will continue to work closely with CVB as we progress down the licening path. What opportunities for training and professional development has the project provided?Objective 1 required development of an in vitro potency assay for our vaccine. This assay, developed in R&D, has been transferred from our research group to technicians in our Quality Assurance group. This required training and expansion of the technician's skillsets. Objective 2 similarly required coordination between R&D and our manufacturing staff. R&D scientists worked hand and hand with production staff and technicians to develop and optimize production-friendly scaleup procedures and worked with staff to ensure their competency with new equipment, reagents and methods. Similar to objective 2, objective 3 required close coordination with R&D, production, QA and regulatory staff to ensure that developed inactivation procedures met technical, quality, manufacturing and regulatory requirements. The final processes have been communicated to staff who have been trained in the procedures. Objectives 4 and 5 saw the research group working closely with swine production system in sourcing and monitoring our research animals used in the study. This also required working with pathologists at ISU to analyze specimens and interpet results. How have the results been disseminated to communities of interest?The licensure phase of this project requires close collaboration with CVB to ensure all procedures are completed. Study results of the licensing phase are communicated to CVB as licensure progresses. Once approval is granted, our marketing and technical service teams will become involved in educating producers and veterinarians on the product. 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 overall focus of phase II was to further develop and commercialize this vaccine to protect pigs from infections by multiple strains or subtypes of SIVs. This project wa comprised of five objectives necessary to achieve USDA-licensure and commercial success. Objective 1, which has been completed, developed an in vitro potency assay necessary for antigen quantification in finished vaccine. Objective 2, which has similarly been completed, focused on the development of robust manufacturing processes to cost-effectively scale antigen production. Objective 3 evaluated and developed inactivation procedures to both ensure inactivation of baculovirus in the final product while maintaining NA antigenicity. Evaluation of duration of vaccine immunity was the focus of objective 4, which was executed from March-August 2021. This was the main focus of year two of this phase two study. The plan was to conduct the experiment for 6 months, but due the unexpectedissuewith challenge strain not causing significant lung lesions in finishing age pigs, the last challenge was conducted at four months.The final objective, objective 5, evaluated potential maternal antibody interference on vaccine efficacy. As expected, our studies demonstrate that the immune response elicited by our vaccine is unaffected by maternal antibodies. This exciting result distinguishes our vaccine from incumbent products and opens the door to vaccination of growing pigs. This two-year SBIR grant has been very successful, with 5/5 objectives completed. With the CVB approval of our masterseed viruses in August of 2021, we are finally able to proceed with additional studiesand furtherance of licensure of the vaccine with the USDA Center for Veterinary Biologics.

Publications

Progress 09/01/19 to 08/31/20

Outputs
Target Audience:The target audience for year 1 of this project is internal stakeholders and externally the USDA Center for Veterinary Biologics. Year 1 is focused on tasks necessary for licensure of the vaccine with USDA. We have been engaged with the CVB during this period and are completing tasks outlined in our project that are necessary for vaccine licensure Changes/Problems:We have not made any significant changes to this project. Objectives 1-3 have been satisfactorily completed and represent significant milestones in the development and licensure of this vaccine. We are continuing to communicate with CVB and are completing additional tasks required for licensure. Objective 5, evaluation of maternal antibody interfence on our vaccine, has likewise successfully been completed. Results from this study demonstrate that maternal antibodies to not interfere with active immunization with our vaccine as we hypothesized. Objective 4, evaluation of duration of immunity, is planned for year 2. We are very pleased with our progress during year 1 with 4 of 5 objectives completed with no significant issues. Our most signficant hurdle for licensure is satisfactorily completing licensing steps as evaluated by CVB. Many of these requirements have a high level of subjectivity and we are working closely with CVB to alleviate any concerns that they have. What opportunities for training and professional development has the project provided?Objective 1 required development of an in vitro potency assay for our vaccine. This assay, developed in R&D, has been transferred from our research group to technicians in our Quality Assurance group. This required training and expansion of the technician's skillsets. Objective 2 similarly required coordination between R&D and our manufacturing staff. R&D scientists worked hand and hand with production staff and technicians to develop and optimize production-friendly scaleup procedures and worked with staff to ensure their competency with new equipment, reagents and methods. Similar to objective 2, objective 3 required close coordination with R&D, production, QA and regulatory staff to ensure that developed inactivation procedures met technical, quality, manufacturing and regulatory requirements. The final processes have been communicated to staff who have been trained in the procedures. How have the results been disseminated to communities of interest?Results from objectives 1-3 have direct bearing on the USDA-licensure of this vaccine and have been communicated to CVB staff. We are working with CVB to obtain vaccine licensure. What do you plan to do during the next reporting period to accomplish the goals?We will continue to work with CVB to complete their requirements for vaccine licensure. Objectives 4 and 5 are largely to test vaccine performance. These studies will be conducted or finalized in year 2 and the results will be utilized by our technical services and marketing groups to communicate vaccine performance to customers (veterinarians and swine producers)

Impacts
What was accomplished under these goals? The overall focus of phase II project is to further develop and commercialize this vaccine to protect pigs from infections by multiple strains or subtypes of SIVs. This project is comprised of five objectives necessary to achieve USDA-licensure and commercial success. Objective 1, which has been completed, developed an in vitro potency assay necessary for antigen quantification in finished vaccine. This innovative assay uses plates coated with the NA inhibitor oseltamivir to capture active NA in the vaccine that is subsequently detected in a quantitative manner using subtype-specific antisera. Objective 2, which has similarly been completed, focused on the development of robust manufacturing processes to cost-effectively scale antigen production. Objective 3 evaluated and developed inactivation procedures to both ensure inactivation of baculovirus in the final product while maintaining NA antigenicity. Evaluation of duration of vaccine immunity is the focus of objective 4 which is planned for the winter of 2020/2021. The final objective 5, evaluated potential maternal antibody interference on vaccine efficacy. As expected, our studies demonstrate that the immune response elicited by our vaccine is unaffected by maternal antibodies. This exciting result distinguishes our vaccine from incumbent products and opens the door to vaccination of growing pigs. The first year of this two-year SBIR grant has been very successful, with 4/5 objectives completed. Year two of this project will focus on the completion of the final objective and furtherance of licensure of the vaccine with the USDA Center for Veterinary Biologics.

Publications