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. |