Modified mRNA vaccines protect against Zika virus infection
By Justin M. Richner, S. Himansu, Kimberly A. Dowd, S. Butler, Vanessa Salazar, J. Fox, J. Julander, William W Tang, S. Shresta, T. Pierson and 2 more. Cell, 2017
862 citations recorded by the source corpus.
SUMMARY 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 (~ 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.
Subfields: Infectious Diseases, Insect Science, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/ed91a473faced9b7c9958a3f9b0ba6f5cc1fd674
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Citations in the corpus
- Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines (2019, neutral): “001 mg per kg).(17,24) In contrast, we observed no detectable protein expression or immunogenicity for DOTAP-containing LNPs (Figure 2A).”
- mRNA Vaccines in the COVID-19 Pandemic and Beyond. (2021, neutral): “A prototype ionizable lipid is Dlin-MC3-DMA (abbreviated MC3), which was used in several preclinical and clinical mRNA-LNP vaccines (54, 56).”
- mRNA vaccines — a new era in vaccinology (2018, methodology): “Finally, the Zika virus vaccine described by Richner et al.(85,112) is also entering clinical evaluation in a combined phase I/II trial (NCT03014089).”
- mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, positive): “mRNA encoding an E protein mutation without a conserved fusion-loop epitope was employed to enhance the safety of the anti-Zika mRNA vaccine and avoid potential ADE risk.(387) Furthermore, mRNA encoding the RBD instead of its parental protein reduced the harmful immune response induced by vaccines.”
- Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. (2019, neutral): “Single low-dose vaccinations have shown to be protective against virus infection.(180,197)”