Format

Send to

Choose Destination
Nature. 2017 Mar 9;543(7644):248-251. doi: 10.1038/nature21428. Epub 2017 Feb 2.

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

Author information

1
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
2
Viral Pathogenesis Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
3
Bioqual Inc., Rockville, Maryland 20850-3220, USA.
4
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA.
5
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
6
Acuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.
7
Diagnostic Medicine and Pathobiology, College of Veterinary Medicine and the Biosecurity Research Institute, Kansas State University, Manhattan, Kansas 66506, USA.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 USA.
9
BioNTech RNA Pharmaceuticals, An der Goldgrube 12, 55131 Mainz, Germany.
10
Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.

PMID:
28151488
PMCID:
PMC5344708
DOI:
10.1038/nature21428
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center