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Publication : Modified mRNA Vaccines Protect against Zika Virus Infection.

First Author  Richner JM Year  2017
Journal  Cell Volume  168
Issue  6 Pages  1114-1125.e10
PubMed ID  28222903 Mgi Jnum  J:241295
Mgi Id  MGI:5901772 Doi  10.1016/j.cell.2017.02.017
Citation  Richner JM, et al. (2017) Modified mRNA Vaccines Protect against Zika Virus Infection. Cell 168(6):1114-1125.e10
abstractText  The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers ( approximately 1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theoretical concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein. This variant 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, should this become a clinically relevant concern.
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