Performing Department
(N/A)
Non Technical Summary
Bird flu viruses, particularly a severe form called H5N1, are causing significant problems for U.S. agriculture and raising public health concerns. These viruses can infect many different animals and have recently caused unexpected outbreaks in dairy cows across 17 states, affecting nearly 1,000 herds. This is particularly concerning because these viruses can sometimes spread from animals to humans. The current situation is unique in that the virus has spread to at least 22 different types of wild mammals, and to dairy cows. This widespread infection in animals could lead to economic losses for farmers and poses potential risks to human health. Our research team aims to address this problem by developing and testing new vaccines for dairy cows that will protect them against this virus, and creating testing methods that can tell the difference between vaccinated and infected animals. This research is important because it will help protect the U.S. food supply, prevent economic losses in the farming industry, reduce the risk of virus spread to humans, and help maintain international trade of agricultural products. By developing these tools, we hope to better protect both animal and human health while supporting the sustainability of U.S. agriculture.
Animal Health Component
50%
Research Effort Categories
Basic
30%
Applied
50%
Developmental
20%
Goals / Objectives
Influenza A viruses have a broad host range and cost the U.S. animal health industry billions of dollars annually. The zoonotic nature of these viruses and their constant spillover from animals to humans pose a significant burden to public health and represent a constant pandemic threat.Over the past two decades, outbreaks of highly pathogenic avian influenza (HPAI), have caused severe economic losses in the U.S.A unique feature of the current HPAI H5N1 panzootic in the U.S. is the frequent spillover of the virus to several wild terrestrial and aquatic mammalian species, with at least 22 wild mammalian species reported to be affected. Notably, spillover of HPAI H5N1was detected in dairy cattle (Bos taurus) in Texas and currently over 978 herds in 17 states have been confirmed positive.The impact of the circulation of HPAI H5N1 in wild birds, its frequent spillover into poultry and, more recently into dairy cows, resulting in sustained transmission in this species, cannot be overemphasized. This underscores the urgency for novel intervention strategies to prevent and control HPAI in this new host species. Effective prevention and control tools would decrease direct economic losses posed by the virus to the dairy industry and decrease the risk that uncontrolled circulation of HPAI in a mammalian species poses to public health. The main goals of our study are:Aim 1: To identify highly immunogenic vectored vaccine platform(s) for influenza A H5N1 and validate companion DIVA diagnostics for use in cattle.Aim 2: To determine the protective efficacy of vectored HPAI H5N1 vaccine candidate in dairy cattle.The work proposed here will have a broad impact and promotesustainability of the US animal health, agriculture and food systems. Outbreaks of HPAI result in substantial economic losses and long-lasting impact to poultry and dairy industries, impairing international trade, and threatening food-security worldwide. Avian influenza has a strong propensity to mutate and cause infections in various animal species and humans thereby posing constant risk for a global pandemic. Thus, the development of a highly effective HPAI vaccines and companion DIVA-diagnostic assays is crucial not only for safeguarding the health and welfare of animals but also for ensuring sustainability of animal agriculture and preventing zoonotic transmission of the virus.
Project Methods
The overall goals of the proposed project is to develop novel vaccine platforms and DIVA compatible companion diagnostic assays for HPAI H5N1 virus and their use in dairy cattle. To achieve these goals we propose two objectives and a series of in vitro and in vivo studies as outlined below.Aim 1: To identify highly immunogenic vectored vaccine platform(s) for influenza A H5N1 and validate companion DIVA diagnostics for use in cattle. We will characterize two vector platforms - Orf vector (OV) and bovine gammaherpesvirus 4 (BH4) - expressing the haemagglutinin gene (HA), neuraminidase (NA) and/or the nucleoprotein (NP) of HPAI. Their immunogenicity and safety will be assessed in cattle in vivo (Aim 1.1). Additionally, DIVA compatible serological assays (indirect and blocking ELISAs or bead-based multiplex assays) (Aim 1.2) will be developed, thus providing a complete tool kit for effective control of HPAI in livestock.Aim 2: To determine the protective efficacy of vectored HPAI H5N1 vaccine candidate in dairy cattle. In Aim 2, the protective efficacy of the newly developed OV-Flu and BH4-Flu platforms will be evaluated in lactating dairy cattle, and the nature and magnitude of elicited immune responses will be characterized.