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Viral Pathogenesis and Vaccine Development

Viral Vaccine Development

DNA immunization offers many advantages over other conventional vaccine delivery vehicles, most importantly the induction of a broad spectrum of immune responses, which is crucial for protection from many diseases.  However, it has generally been more difficult to induce immune responses in large animal than in mice, the most frequently used model.  We are conducting reserach to evaluate DNA vaccine formulations against large animal diseases such as bovine viral diarrhea virus (BVDV).


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Between 1-3% of the world's population (~170 million people) are infected with Hepatitis C virus (HCV). Acute infection is often insidious and ~80% of infected people remain chronic carriers. Persistent infection eventually results in either mild chronic hepatitis or extensive liver damage. Our research focuses on characterizing the effects of HCV on human dendritic cells and optimizing the functional properties of DCs by treatment with immunomodulatory compounds.


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Currently no prophylactic or therapeutic vaccines for hepatitis C exist.  Therapy involving interferon and ribavirin is very costly, yet ineffective in about half of the patients. There is an urgent need for a better understanding of the molecular mechanisms of hepatitis C viral pathogenesis and to address this, we are studying molecular mechanisms of HCV-associated steatosis and protein translational control.


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No vaccines are currently available for respiratory syncytial virus (RSV), the leading cause of bronchiolitis and viral pneumonia in infants.   Newborn calves suffer from bovinve RSV (BRSV), an infection that closely mimics RSV in infants.  We are examining bovine lung tissue to analyze gene and protein expressions patterns related to BRSV infection. We are also investigating vaccine formulations - testing various immunomodulatory compounds for their ability to induce a Th1-type or balanced response and/or act as mucosal adjuvants for neonatal immunization to RSV.


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Porcine reproductive and respiratory syndrome (PRRS) costs Canadian and American swine industries ~$100 million and ~$560 million annually and the current vaccine has significant shortcomings.  Our research utilizes new technologies associated with reverse genetics to develop a safe, effective and differential vaccine against PRRSV infection.


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Measles remains a major cause of children deaths worldwide but the current measle vaccine has several limitations. We are testing two new vaccine candidates - an adenoviral vaccine and a recombinant protein vaccine formulated with novel adjuvants - that enhance and improve quality of the immune responses to the vaccines.


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Globally bovine herpesvirus-1 (BHV-1) causes a number of diseases in cattle and is an important factor in shipping fever. BHV-1 also contributes to abortion, stillbirths and calf mortality and infectious bovine rhinotracheitis caused by BHV-1 causes death in up to 10% of infected animals.   Our research examines BHV-1 replication and molecular mechanisms associated with the tegument region. We are evaluating the role of tegument proteins in the viral infectious process, the viral replication cycle stage affected, intracellular trafficking properties during viral infection and potential intracellular interactions.


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Members of this Research Group

 

Program Manager: Sylvia van den Hurk

Scientists: Qiang Liu, Alexandre Zakhartchouk, Joyce Wilson

Technicians: Laura Latimer, Shirley Hauta, Marlene Snider

Graduate Students: Tara Donovan, Sarah Mackenzie-Dyck, Ellen Watkiss, Brett Hoffman, Patricia Thibault (McGee), Adam Huys

Post doctoral Fellows:  Tayyaba Baig 

 


Awards, Publications, Links

 Below are some sample publications for this research group.  More information can be obtained in Publications and Patents.

  • C. Jackel-Cram, L. Qiao, Z. Xiang, R. Brownlie, Y. Zhou, L. Babiuk, and Q. Liu. 2010. Hepatitis C virus genotype-3a core protein enhances sterol regulatory element binding protein-1 activity through the PI3K-Akt-2 pathway. Journal of General Virology, published February 3, 2010.
  • Q. Liu. 2010. Molecular mechanisms of fatty liver disease associated with hepatitis C virus infection. Stem Cell Research Journal, accepted February 11, 2010.

Research Partners

 

VIDO-InterVac acknowledges the organizations that have provided funding for this research: