Performing Department
(N/A)
Non Technical Summary
Influenza A viruses (IAV) pose a serious threat to both animal and human health. Pigs are especially vulnerable because they can be infected with IAV viruses from birds, humans, and other pigs, allowing new, potentially pandemic strains to emerge. The recent spread of H5N1 bird IAV in poultry, cattle, and even humans in the U.S. raises urgent concerns, especially with evidence showing that H5N1 can also infect pigs. Current swine IAV vaccines are often outdated and ineffective against new strains and, most importantly, they only provide a short duration of protection that usually wanes by 2 months post-boost, leaving pigs and humans at risk. This project aims to develop a broadly protective, next-generation IAV vaccine for pigs to reduce these risks, protect public health, and support the pork industry.We will use advanced computer modeling to design vaccine components that protect against a wide variety of IAV strains. These will be tested in pigs to assess how quickly, how well, and how long they work, including whether they prevent illness and transmission. Our team will also train students and postdocs in modern vaccine research and share results with scientists, industry, and public health officials. Ultimately, this project aims to reduce the risk of future IAV pandemics by stopping dangerous viruses in pigs before they can spread to people. It will also strengthen animal health, reduce economic losses, and serve as a model for improving vaccines across species.
Animal Health Component
33%
Research Effort Categories
Basic
34%
Applied
33%
Developmental
33%
Goals / Objectives
The primary goal of this project is to develop and validate a universal swine influenza vaccine using epitope-optimized Epigraph immunogens that are designed to induce broad, cross-reactive immunity against genetically diverse H1, H3, and H5 swine influenza A viruses (IAV). The current commercial and autogenous vaccines often fail due to strain mismatches and our project aims to ameliorate those weaknesses by provide long-lasting protection in swine, mitigate economic losses in the pork industry, and reduce the risk of zoonotic spillover and potential pandemics originating from swine, a key mixing vessel for influenza viruses.Inpursuit of this goal, we have engineered computationally designed Epigraph immunogens that are based on comprehensive global influenza sequence data that ensures the maximum coverage of protective T and B cell epitopes. These immunogens will be tested in swine for immunogenicity and durability, evaluating both humoral and cellular immune responses. Ultimately the vaccines will be tested in stringent virus challenge studies in pigs using divergent strains from major clades in order to demonstrate broadly protective efficacy. Additionally, a parallel study will assess the capacity of H5 Epigraph immunogens to prevent avian influenza transmission to pigs, further reducing the risk of reassortment and interspecies transmission.The impact of this vaccine project will also be augmented by investigating the impact of serotype switching between adenoviral vectors (Ad5 and Ad6) to enhance vaccine-induced immunity. This strategy, tested through homolgous and heterologous prime-boost regimens, will assess how quickly and durably immunity is established and maintained. Our novel vaccine candidates will be benchmarked against the commercial vaccine FluSure-XP, ensuring comparative evaluation of efficacy, breadth of immune coverage, and protective outcomes. IN keeping with reproducibility guidelines, we will employ rigorous protocol that will ensure statistical significance, reproducibility, and transparency. Swine from multiple sources will be used, and all reagents and data will be made available to non-profit institutions upon request. Ultimately, this project aligns with USDA priorities and holds the potential to revolutionize swine influenza vaccination while advancing methodologies applicable to other rapidly evolving viruses.
Project Methods
This project will be performed using a combination of experimental research and interdisciplinary collaboration, with a strong foundation in virology, immunology, and veterinary science. We will administer novel viral vectored vaccines that are designed to maximize the breadth of immunity to swine and then assess its safety and immunogenicity through viral challenge studies. In order to analyze the results, we will collect virological, immunological, and clinical data, that will be analyzed using statistical and computational methods. This includes measuring viral shedding, antibody responses, and cell-mediated immunity. Results will be evaluated to determine both the effectiveness of the vaccine in preventing infection and the likelihood of onward transmission. We will include hands-on research for graduate and postdoctoral trainees, with mentored experiences in laboratory and field settings. The trainees will gain technical and regulatory knowledge, enhancing their future contributions to animal and public health. Our project also involves outreach activities such as presentations at scientific conferences and institutional briefings to communicate findings and promote adoption of vaccine technologies.The metrics of the project's impact will involve tracking several quantitative indicators, including the immune response metrics in vaccinated swine, reduction in transmission rates, the number of students trained, and the dissemination of findings through peer-reviewed publications and public presentations. The success and progress of each of the specific aims will be determined by the successful publication of manuscripts and feedback from the scientific and agricultural community. The effectiveness of training and outreach efforts will be assessed through participant feedback and follow-up engagement metrics. We will ensure that the outcomes align with the descibed goals of advancing scientific understanding and improving disease prevention in swine populations.