Format

Send to

Choose Destination
Cell. 2017 Mar 9;168(6):1114-1125.e10. doi: 10.1016/j.cell.2017.02.017. Epub 2017 Feb 17.

Modified mRNA Vaccines Protect against Zika Virus Infection.

Author information

1
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Valera LLC, a Moderna Venture, 500 Technology Square, Cambridge, MA, 02139, USA.
3
Viral Pathogenesis Section, National Institutes of Health, Bethesda, MD 20892 USA.
4
Institute for Antiviral Research, Utah State University, Logan, UT, 84335 USA.
5
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
6
Valera LLC, a Moderna Venture, 500 Technology Square, Cambridge, MA, 02139, USA. Electronic address: Giuseppe.Ciaramella@Valeratx.com.
7
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.

Abstract

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.

KEYWORDS:

Dengue virus; RNA vaccine; Zika virus; antibody neutralization; flavivirus; immunity; pathogenesis; protection

PMID:
28222903
PMCID:
PMC5388441
DOI:
10.1016/j.cell.2017.02.017
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center