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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Injections, Intradermal
  • Macaca mulatta / immunology
  • Macaca mulatta / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • RNA Stability
  • RNA, Messenger / administration & dosage*
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • RNA, Viral / administration & dosage
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Time Factors
  • Vaccination
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology*
  • Zika Virus / chemistry
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Glycoproteins
  • RNA, Messenger
  • RNA, Viral
  • Viral Envelope Proteins
  • Viral Vaccines