Sharif’s project took a systemic approach to understanding avian influenza virus (AIV) and developing robust prevention strategies. The team developed an AIV vaccine that harnesses natural immune-response mechanisms to fight against the virus and reduce transmission among poultry.
Avian influenza virus (AIV) is a significant pathogen affecting livestock poultry with growing implications for human health. Outbreaks of AIV lead to substantial economic losses in the poultry industry due to the culling of birds required to control the spread of infection. Beyond its impact on the poultry industry, AIV is classified as a zoonotic disease, capable of transferring between animals and humans via respiratory and oral-fecal routes. Current AIV management strategies focus on the implementation of stringent biosecurity protocols coupled with the use of vaccines. However, gaps remain in the availability of effective and reliable vaccines, and comprehensive disease control measures are still lacking. Despite this, vaccines have proven to be an effective tool in managing AIV outbreaks. Developing more robust vaccines can help reduce the transmission of the virus both within flocks and between different populations. Given the complex and dynamic nature of AIV transmission, the development of novel vaccination strategies must be informed by detailed transmission models, making use of widespread data related to AIV monitoring and outbreaks. These models are crucial for evaluating the efficacy of new vaccines and optimizing strategies for disease control and understanding the complexity of transmission for better management.
Dr. Shayan Sharif and his research team addressed this issue in an interdisciplinary project aimed at developing a better system for detecting and managing outbreaks from the farm level to the global scale. To address this objective, Sharif’s team primarily focused on the development of new and efficacious vaccines to control AIV transmission in chicken flocks. Building on previous research, Sharif’s team developed a novel vaccine and tested the efficacy and cost-savings of vaccinating at earlier life stages, including in ovo (in egg). A second part of the project was creating a decision support framework for predicting AIV outbreak risks and assessing the impact of vaccination on virus transmission. Finally, Sharif’s team studied the dynamics of AIV transmission and the effects of varied vaccination strategies on the spread of the virus. The team began by modeling AIV transmission with a focus on virus flow through two distinct routes: respiratory (aerosol) and oral-fecal (contaminated materials). Modelling frameworks played an important role in the research, serving to both optimize vaccine strategies and to develop a decision support system (DSS) tool that can offer valuable insights into controlling AIV outbreaks and optimizing vaccination strategies.
A key aspect of this research project was the development of a novel, immune-based vaccine strategy to help control the spread of AIV. The team investigated the potential of combining probiotic bacteria and toll-like receptor (TLR) ligands as components of a vaccine designed to enhance the host immune response. This vaccine also includes an inactivated form of the AIV, which, when administered, triggers the immune system to protect against current and future infections. The inactivated virus stimulates the immune system, while TLR ligands—molecules that interact with immune cells—serve as an adjuvant that further strengthens this response. Early in the project, the team found that when AIV-positive chickens were given a low dose of a specific TLR ligand, they showed significantly lower rates of cloacal shedding (fecal transmission), one of the primary pathways for the virus to spread. Building on this discovery, Sharif’s team developed a vaccine that addresses both respiratory and oral-fecal transmission routes of the virus. This vaccine is characterized by its high immunogenicity, meaning it effectively provokes a strong, lasting immune response in the host.
The project findings build upon previous vaccination strategies for AIV by developing immune-based vaccines that enhance or direct the immune system’s response to the virus. These vaccines offer several advantages over earlier approaches, including cost-effectiveness and adaptability to emerging strains, potentially providing protection against more lethal variants. When combined with immune-boosting additives such as TLR ligands, they also offer long-term protection. Additionally, the team’s work on vaccination and transmission pathway modeling advances current disease control efforts by adopting a systematic approach to reducing AIV transmission. This research is crucial for mitigating the significant economic impact of outbreaks, which can result in the culling of millions of birds and financial losses in the poultry industry. Beyond economic costs, outbreaks also damage public perception of food safety and disrupt supply chains due to lost poultry exports, affecting the livelihoods of producers. Given the increasing frequency of AIV outbreaks, developing more effective control strategies is more urgent than ever.
Alkie, T. N., Taha-Abdelaziz, K., Barjesteh, N., Bavananthasivam, J., Hodgins, D. C., & Sharif, S. (2017). Characterization of Innate Responses Induced by PLGA Encapsulated- and Soluble TLR Ligands In Vitro and In Vivo in Chickens. PLOS ONE, 12(1), e0169154. https://doi.org/10.1371/journal.pone.0169154
Alkie, T. N., Yitbarek, A., Taha-Abdelaziz, K., Astill, J., & Sharif, S. (2018). Characterization of immunogenicity of avian influenza antigens encapsulated in PLGA nanoparticles following mucosal and subcutaneous delivery in chickens. PLOS ONE, 13(11), e0206324. https://doi.org/10.1371/journal.pone.0206324
Alqazlan, N., Alizadeh, M., Boodhoo, N., Taha-Abdelaziz, K., Nagy, E., Bridle, B., & Sharif, S. (2020). Probiotic Lactobacilli Limit Avian Influenza Virus Subtype H9N2 Replication in Chicken Cecal Tonsil Mononuclear Cells. Vaccines, 8(4), 605. https://doi.org/10.3390/vaccines8040605
Alqazlan, N., Astill, J., Raj, S., & Sharif, S. (2022). Strategies for enhancing immunity against avian influenza virus in chickens: A review. Avian Pathology, 51(3), 211–235. https://doi.org/10.1080/03079457.2022.2054309
Alqazlan, N., Astill, J., Taha-Abdelaziz, K., Nagy, É., Bridle, B., & Sharif, S. (2021). Probiotic Lactobacilli Enhance Immunogenicity of an Inactivated H9N2 Influenza Virus Vaccine in Chickens. Viral Immunology, 34(2), 86–95. https://doi.org/10.1089/vim.2020.0209
Astill, J., Alkie, T., Yitbarek, A., Taha-Abdelaziz, K., Bavananthasivam, J., Nagy, É., Petrik, J. J., & Sharif, S. (2018a). Examination of the effects of virus inactivation methods on the induction of antibody- and cell-mediated immune responses against whole inactivated H9N2 avian influenza virus vaccines in chickens. Vaccine, 36(27), 3908–3916. https://doi.org/10.1016/j.vaccine.2018.05.093
Astill, J., Alkie, T., Yitbarek, A., Taha-Abdelaziz, K., Bavananthasivam, J., Nagy, É., Petrik, J. J., & Sharif, S. (2018b). Induction of immune response in chickens primed in ovo with an inactivated H9N2 avian influenza virus vaccine. BMC Research Notes, 11(1), 428. https://doi.org/10.1186/s13104-018-3537-9
Astill, J., Alkie, T., Yitbarek, A., Taha-Abdelaziz, K., Shojadoost, B., Petrik, J. J., Nagy, É., & Sharif, S. (2018). A Comparison of Toll-Like Receptor 5 and 21 Ligands as Adjuvants for a Formaldehyde Inactivated H9N2 Avian Influenza Virus Vaccine in Chickens. Viral Immunology, 31(9), 605–612. https://doi.org/10.1089/vim.2018.0072
Astill, J., Dara, R. A., Campbell, M., Farber, J. M., Fraser, E. D. G., Sharif, S., & Yada, R. Y. (2019). Transparency in food supply chains: A review of enabling technology solutions. Trends in Food Science & Technology, 91, 240–247. https://doi.org/10.1016/j.tifs.2019.07.024
Barjesteh, N., Taha-Abdelaziz, K., Kulkarni, R. R., & Sharif, S. (2019). Innate antiviral responses are induced by TLR3 and TLR4 ligands in chicken tracheal epithelial cells: Communication between epithelial cells and macrophages. Virology, 534, 132–142. https://doi.org/10.1016/j.virol.2019.06.003
Bavananthasivam, J., Astill, J., Matsuyama-Kato, A., Taha-Abdelaziz, K., Shojadoost, B., & Sharif, S. (2021). Gut microbiota is associated with protection against Marek’s disease virus infection in chickens. Virology, 553, 122–130. https://doi.org/10.1016/j.virol.2020.10.011
Bridle, B. W. (2020). Fast COVID-19 vaccine timelines are unrealistic and put the integrity of scientists at risk. In The Canadian Press. Canadian Press Enterprises Inc.
Bridle, B. W., University of Guelph, Mubareka, S., University of Toronto, & Sharif, S. (2020). Training our immune systems: Why we should insist on a high-quality COVID-19 vaccine. In The Canadian Press. Canadian Press Enterprises Inc.
Bridle, B. W. (2020). Why vaccines are less effective in the elderly, and what it means for COVID-19. In The Canadian Press. Canadian Press Enterprises Inc.
Raj, S., Alizadeh, M., Shoojadoost, B., Hodgins, D., Nagy, É., Mubareka, S., Karimi, K., Behboudi, S., & Sharif, S. (2023). Determining the Protective Efficacy of Toll-Like Receptor Ligands to Minimize H9N2 Avian Influenza Virus Transmission in Chickens. Viruses, 15(1), 238. https://doi.org/10.3390/v15010238
Raj, S., Astill, J., Alqazlan, N., Boodhoo, N., Hodgins, D. C., Nagy, É., Mubareka, S., Karimi, K., & Sharif, S. (2022). Transmission of H9N2 Low Pathogenicity Avian Influenza Virus (LPAIV) in a Challenge-Transmission Model. Vaccines, 10(7), 1040. https://doi.org/10.3390/vaccines10071040
Raj, S., Matsuyama-Kato, A., Alizadeh, M., Boodhoo, N., Nagy, E., Mubareka, S., Karimi, K., Behboudi, S., & Sharif, S. (2023). Treatment with Toll-like Receptor (TLR) Ligands 3 and 21 Prevents Fecal Contact Transmission of Low Pathogenic H9N2 Avian Influenza Virus (AIV) in Chickens. Viruses, 15(4), 977. https://doi.org/10.3390/v15040977
Shojadoost, B., Kulkarni, R. R., Yitbarek, A., Laursen, A., Taha-Abdelaziz, K., Negash Alkie, T., Barjesteh, N., Quinteiro-Filho, W. M., Smith, T. K., & Sharif, S. (2019). Dietary selenium supplementation enhances antiviral immunity in chickens challenged with low pathogenic avian influenza virus subtype H9N2. Veterinary Immunology and Immunopathology, 207, 62–68. https://doi.org/10.1016/j.vetimm.2018.12.002
Xie, X.-T., Yitbarek, A., Astill, J., Singh, S., Khan, S. U., Sharif, S., Poljak, Z., & Greer, A. L. (2021). Within-host model of respiratory virus shedding and antibody response to H9N2 avian influenza virus vaccination and infection in chickens. Infectious Disease Modelling, 6, 490–502. https://doi.org/10.1016/j.idm.2021.02.005
Xie, X.-T., Yitbarek, A., Uddin Khan, S., Sharif, S., Poljak, Z., & Greer, A. L. (2020a). A within-host mathematical model of H9N2 avian influenza infection and type-I interferon response pathways in chickens. Journal of Theoretical Biology, 499, 110320. https://doi.org/10.1016/j.jtbi.2020.110320
Xie, X.-T., Yitbarek, A., Uddin Khan, S., Sharif, S., Poljak, Z., & Greer, A. L. (2020b). A within-host mathematical model of H9N2 avian influenza infection and type-I interferon response pathways in chickens. Journal of Theoretical Biology, 499, 110320. https://doi.org/10.1016/j.jtbi.2020.110320
Yitbarek, A., Alkie, T., Taha-Abdelaziz, K., Astill, J., Rodriguez-Lecompte, J. C., Parkinson, J., Nagy, É., & Sharif, S. (2018). Gut microbiota modulates type I interferon and antibody-mediated immune responses in chickens infected with influenza virus subtype H9N2. Beneficial Microbes, 9(3), 417–428. https://doi.org/10.3920/BM2017.0088
Yitbarek, A., Astill, J., Hodgins, D. C., Parkinson, J., Nagy, É., & Sharif, S. (2019). Commensal gut microbiota can modulate adaptive immune responses in chickens vaccinated with whole inactivated avian influenza virus subtype H9N2. Vaccine, 37(44), 6640–6647. https://doi.org/10.1016/j.vaccine.2019.09.046
Yitbarek, A., Taha-Abdelaziz, K., Hodgins, D. C., Read, L., Nagy, É., Weese, J. S., Caswell, J. L., Parkinson, J., & Sharif, S. (2018). Gut microbiota-mediated protection against influenza virus subtype H9N2 in chickens is associated with modulation of the innate responses. Scientific Reports, 8(1), 13189. https://doi.org/10.1038/s41598-018-31613-0
Yitbarek, A., Weese, J. S., Alkie, T. N., Parkinson, J., & Sharif, S. (2018). Influenza A virus subtype H9N2 infection disrupts the composition of intestinal microbiota of chickens. FEMS Microbiology Ecology, 94(1). https://doi.org/10.1093/femsec/fix165
Yousefinaghani, S., Dara, R. A., Poljak, Z., & Sharif, S. (2020). A decision support framework for prediction of avian influenza. Scientific Reports, 10(1), 19011. https://doi.org/10.1038/s41598-020-75889-7
Yousefi Naghani, S., Dara, R., Poljak, Z., & Sharif, S. (2019). A review of knowledge discovery process in control and mitigation of avian influenza. Animal Health Research Reviews, 20(1), 61–71. https://doi.org/10.1017/S1466252319000033
Yousefinaghani, S., Dara, R., Poljak, Z., Bernardo, T. M., & Sharif, S. (2019a). The Assessment of Twitter’s Potential for Outbreak Detection: Avian Influenza Case Study. Scientific Reports, 9(1), 18147. https://doi.org/10.1038/s41598-019-54388-4
Yousefinaghani, S., Dara, R., Poljak, Z., Bernardo, T. M., & Sharif, S. (2019b). The Assessment of Twitter’s Potential for Outbreak Detection: Avian Influenza Case Study. Scientific Reports, 9(1), 18147. https://doi.org/10.1038/s41598-019-54388-4
Yousefinaghani, S., Dara, R., Poljak, Z., Song, F., & Sharif, S. (2021). A framework for the risk prediction of avian influenza occurrence: An Indonesian case study. PLOS ONE, 16(1), e0245116. https://doi.org/10.1371/journal.pone.0245116
Dr. Zvonimir Poljak, Dr. Amy Greer, Dr. Shahriar Behboudi, Dr. Faizal Careem, Dr. Evan Fraser, Dr. Heba Atalla, Dr. Bahram Shojadoost, Dr. Jake Astill, Dr. Grazieli Maboni
Sugandha Raj, Nadiyah Alqazlan, Ayumi Matsuyama, Dylan Melmer, Kaushalya Kuruppu, Emmy Luo, Xiao Xie, Fatemeh Fazel, Sheila Keay, Leilani Rocha, Famke Alberts, Wendy Xie, Isha Berry, Mohammad Amiri-Zarandi, Dr. Hiroshi Iseki, Dr. Nitish Boodhoo, Dr. Mohammadali Alizadeh, Dr. Mehdi Hazrati
The Pirbright Research Institute, Canadian Poultry Research Council, Chicken Farmers of Saskatchewan, Egg Farmers of Canada, Natural Sciences and Engineering Research Council of Canada, Ontario Ministry of Agriculture, Food and Agribusiness
