Philadelphia University + Thomas Jefferson University

Research Projects

Research Projects

Vaccines against emerging viral diseases

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Antibody dependent cellular phagocytosis of target cells (green) by macrophages (red). In a) macrophages have successfully phagocytized or trogocytized target cells that were expressing a viral glycoprotein in the presence of antibody (left, 80X magnification; right, 40X magnification). b) and c) are negative controls.

A) Rhabdovirus-based vectors as vaccines against other infectious diseases.

  • Rabies virus (RABV)-based vaccines are promising as both live and killed vaccines against infectious disease. This is based on the finding that RABV vectors are highly immunogenic and combine a necessary vaccine with limited financial resources for development (such as several hemorrhagic fever viruses) with a safe, approved, and financially practical vaccine (rabies).
  • Using different molecular and immunological approaches, we perform detailed studies of highly attenuated RABV expressing and incorporating immunogenic proteins of emerging infectious diseases. Most advanced is the development of our filovirus (e.g. Ebola Virus (EBOV), Sudan virus (SUDV) and Marburg virus (MARV)) vaccine. In the pre-clinical phase of development are novel vaccines against Hendra virus, Nipah virus, Lassa virus, Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) and Zika virus.
  • The goal is the development of this vaccine platform not only for human use but also to immunize animals to break the transmission cycle of these zoonotic diseases. 
  • Development of safer and more potent vaccines for wildlife and human rabies.
  • Development of novel vaccines against lyssaviruses (rabies-related viruses) from which the current rabies vaccine does not protect.

 

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Measles vaccine vector expressing ZIKV prME i) before the N gene( MV-E0) ii) between the N and P genes (MV-E2) were generated. Vero cells infected with MV-E0 or MV-E2 and controls: a) parent Measles vector expressing GFP before N (MV-GFP0) b) ZIRAB (RABV based Zika vaccine) was characterized by immunofluorescence assay with MV-M protein stained in Green and Zika E protein stained in Red.

B) Measles-based vectors as vaccines against other infectious diseases.

  • Recently, the laboratory has begun utilizing a novel measles virus-based vaccine vector. The measles vector protects not only against measles but can also be designed to protect against other infectious diseases. Measles vaccines have been safely delivered to more than 100 million children, it is such a vaccine could have a great impact. Most advanced in ourt laboratory is the development of a save measles virus vaccine with dual efficacy against Zika virus and measles.

 

 

 


Pathogenicity and Neurovirology

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Ifit2 protects B6 mice from RABV neuropathogenesis after intranasal infection. Overall survival of wild-type, Ifit1-/-, Ifit2-/-, and Ifnar-/- mice after intranasal infection with 104 to 105 FFU of RABV is shown (n = number of animals). Statistical significance is indicated by asterisks or "ns" (not significant) above the curve (wild type versus Ifit1-/-, P = 0.09; wild-type versus Ifit2-/-, P = 0.0002; wild-type versus Ifnar-/-, P = 0.0045).

We are interested in a detailed understanding of the biochemistry, molecular biology and immunology of rabies virus and its interaction with the infected host. We also use rabies virus as a tool for neuroanatomy

  • Innate immunity (e.g. the interferon sensitive Ifit genes) and their function for RABV virus neurotropism and neuroinvasiveness
  • Immune responses to RABV in the infected host (innate and adaptive)
  • Antiviral drugs against lyssaviruses

Development of transneuronal tracing with rabies virus