Featuring speaker Dr. Justin Richner, this livestream will explore advances in mRNA Vaccine Therapies in the fields of Cancer Immunotherapy and Infectious Diseases.
Dr. Justin M. Richner
Assistant Professor, Department of Microbiology & Immunology
University of Illinois Chicago
Dr. Richner earned his doctoral degree from the University of California at Berkeley under the mentorship of Dr. Britt Glaunsinger. He performed his post-doctoral studies at Washington University in St. Louis with Dr. Michael Diamond studying viral immunology and vaccine development. In this setting he developed, in collaboration with Moderna, a Zika virus vaccine with the novel mRNA-lipid nanoparticle gene therapy platform.
Abstract:
The emergence of Zika virus (ZIKV) infection has prompted a global effort to develop safe and effective vaccines. Recent technological advances have led to a number of promising vaccine platforms including antigen-coding mRNA vaccines encapsidated in a lipid nanoparticle (mRNA-LNP). We engineered an mRNA-LNP vaccine encoding for ZIKV prM-E structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs resulted in high neutralizing antibody titers that protected against ZIKV infection and conferred sterilizing immunity. Vaccinated dams challenged with a heterologous ZIKV strain showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. Zika infection induces cross-reactive antibodies that can enhance Dengue virus (DENV) infection. To limit the generation of these cross-reactive antibodies, we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein. This variant vaccine protected against ZIKV and diminished production of antibodies enhancing DENV infection in cells or mice. A modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of sensitizing individuals to subsequent exposure to DENV. Our lab is further refining the mRNA-LNP vaccines to overcome immunesuppression and combat infectious diseases which have proven a significant challenge to traditional vaccine development.
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