Zika Virus Protection by a Single Low-dose Nucleoside-modified MRNA Vaccination

Overview

Journal Nature

Specialty Science

Date 2017 Feb 3

PMID 28151488

Citations 443

Authors

Norbert Pardi

Michael J Hogan

Rebecca S Pelc

Hiromi Muramatsu

Hanne Andersen

Christina R DeMaso

Kimberly A Dowd

Laura L Sutherland

Richard M Scearce

Robert Parks

Wendeline Wagner

Alex Granados

Jack Greenhouse

Michelle Walker

Elinor Willis

Jae-Sung Yu

Charles E McGee

Gregory D Sempowski

Barbara L Mui

Ying K Tam

Yan-Jang Huang

Dana Vanlandingham

Veronica M Holmes

Harikrishnan Balachandran

Sujata Sahu

Michelle Lifton

Stephen Higgs

Scott E Hensley

Thomas D Madden

Michael J Hope

Katalin Kariko

Sampa Santra

Barney S Graham

Mark G Lewis

Theodore C Pierson

Barton F Haynes

Drew Weissman

Affiliations

Soon will be listed here.

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.

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