Research

Research

During the past 20 years, Prof. Fang’s research has been focused on understanding the basic molecular mechanisms of viral pathogenesis, and applying the basic knowledge to develop vaccines and diagnostic assays. Current projects are directed to elucidate the persistent infection mechanism of swine arterivirus (PRRSV), develop novel mRNA-based influenza vaccine, and validate field-deployable nanosensor-based diagnostic assays for emerging swine viral pathogens. These projects have been supported by US Department of Agriculture (USDA), National Institute of Health (NIH), National Pork Board (NPB) and Swine Health Information Center (SHIC).  

Current Research Projects

1. Fang Y., Huber V., Tomich J. A broadly protective vaccine and novel delivery platform for influenza A virus. (USDA-NIFA grant #2025-39601-44645)
   Influenza A viruses (IAV) cause significant economic loss in livestock industry. The zoonotic nature of the virus also pose a significant pandemic threat to human population. Pigs have long been considered a mixing vessel for generation of novel influenza viruses. The recent emergence and outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus in mammals, especially in dairy cows, have increased concern of IAV panzootic/pandemic in animals and human population. A universal vaccine that can induce strong, broadly protective immunity against genetically diversified viral strains is urgently needed. The overall goal of this project is to develop a broadly protective influenza mRNA vaccine using chimeric HAs and emerging H5 as immunogens and novel nanoparticles as the deliver agent. We expect this “cocktail” vaccine will induce a broad protection against a wide range of influenza virus subtypes, which could serve as an important tool in preparedness plan for potential outbreaks of HPAI H5N1 in human and animal species.
2. Fang Y., Zhang WP. Development of a novel epitope-based vaccine candidate for FMDV. (USDA-ARS grant #58-3022-3020)
   Foot-and-mouth disease virus (FMDV) is the etiologic agent of FMD, a disease of cloven-hoofed animals. FMDV is genetically highly variable, which is classified into seven distinct serotypes. Strict trading policies and use of inactivated virus vaccine has helped controlling the disease from many countries; however, FMD remains endemic in most of the world, while occasional outbreaks in previously declared FMD-free regions may cause economic devastation. There is a need for novel strategies for controlling this disease. The goal of this project is to develop a broadly protective FMDV vaccine candidate using non-toxic enterotoxin and E. coli as the adjuvant-delivery system.
3. Fang Y. Molecular mechanisms of PRRSV persistence: Identification and targeting viral-host signatures for disease surveillance and prevention. (USDA-NIFA grant #2023-67015-39079)
   Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important swine pathogens around the world. PRRSV persistence is an important factor impeding disease control and prevention. A significant problem facing the field is that some pigs with asymptomatic persistent infection can transmit the infection to other contact naïve pigs. Current PRRSV diagnostic methods are unable to specifically identify persistently infected animals. The overall goal of this project is to identify host and viral signatures associated with the persistent infection of porcine reproductive and respiratory syndrome virus (PRRSV). The basic knowledge generated from this study will be applied for developing diagnostic assays to specifically detect PRRSV persistently infected pigs. 
4. Fang Y. et al. Novel diagnostic tools and animal model system for study human/animal interface of COVID-19. (NIH/NIAID grant #R01- AI66791)
   Recent studies by us and others identified felid animals, including domestic cats, tigers and lions as highly susceptible to SARS-CoV-2 infection. These findings cause great concerns on the potential for human-to-animal and animal-to-human transmission, along with the virus mutations that appear as the virus goes back and forth between species. One goal of this study is to design and prepare novel reagents and assays for detection and surveillance in animals. A second goal is to develop a feline animal model. Together, these data will be incorporated into epidemiological models for understanding the risk of animal infection for veterinarians, other animal care professionals, and the general public.
5. Paprotny I., Fang Y. et al. Development and validation of a “Smoke Detector” technology for onsite monitoring of emerging viruses in swine farms. (Swine Health Information Center grant #24-078)
   Swine farming is a sector of U.S. livestock industry. Viral pathogens, including PRRSV, IAV, and porcine epidemic diarrhea virus (PEDV) have led to significant economic losses that affect both individual farmers and the global pork industry. The ability of the virus to survive in various environmental conditions underscores the urgent need for improved surveillance and prevention strategies. There is a pressing need for advanced, robust, and automated monitoring systems, which can be installed in swine farms for real-time pathogen detection to rapidly stop disease outbreaks. The goal of this project is to adapt the bioAerium platform, a real-time detector for airborne viral pathogens for rapid sensing of airborne swine viruses, including PRRSV, IAV, and PEDV in farm settings.
6. Wang X., Fang Y. Rapid, inexpensive, simple, and sensitive on-farm detection of PEDV and PDCoV infections. (National Pork Board grant #PR-006214)
   During the past two decades, coronaviruses (CoVs) have been moving into the spotlight by their devastating impact on both human and animal health. In the US, porcine epidemic diarrhea (PED) virus (PEDV) and porcine deltacoronavirus (PDCoV) are newly emerging or re-emerging viral pathogens that have been causing significant economic losses in swine industry. An efficient way to control CoVs is rapid detection of infected animals and subsequently implement quarantine and elimination procedures. Thus, highly sensitive and field deployable on-site diagnostic assays are urgently needed. The goal of this project is to develop a field deployable DNA nanostructure-enabled lateral flow assay for multiplex detection of PEDV and PDCoV infections. 
7. Cunningham B., Fang Y., Shi J. Portable, rapid, sensitive, and inexpensive point-of-use biosensor technology and assays for on-farm detection of ASFV infection. (USDA-NIFA grant #2024-67021-42825)
   Historically, the greatest threats to the US swine production are from foreign animal diseases, such as African swine fever (ASF). ASF is caused by ASF virus (ASFV), which can cause excessive morbidity and mortality in domestic pigs. Current outbreaks of ASFV in Asia, Caribbeans and some European countries pose a potential pandemic threat to the US and global swine industry. There is an urgent need to develop advanced technologies that are capable of providing sensitive and specific assays using simple methods and inexpensive instrumentation, which will enable the tests to be performed in field/farm environments with results obtained immediately. The overall goal of this project is to develop portable, rapid, sensitive, and inexpensive point-of-use biosensor technology and assays for on-farm detection of ASFV infection in aid of field surveillance and outbreak diagnosis.
8. Fang Y., Cunningham B., Shi J. Smartphone-linked field deployable test for African swine fever virus. (USDA-Hatch grant #888974)
   The current paradigm for ASFV surveillance mainly depends on laboratory-based assays, including Enzyme Linked Immunosorbent Assays (ELISA) serological assay for detecting host antibody response and Polymerase Chain Reaction (PCR) test for detecting viral nucleic acid in serum and other samples. The conventional assays are insufficient for field outbreak situations, due to the complex workflows, high cost, and lengthy sample-to-answer time. The goal of this project is to validate a field deployable smart phone-linked PathTracker test for rapid detection of ASFV infection in the field.