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

被引：677

作者：

Pardi, Norbert ^{[1
]}

Hogan, Michael J. ^{[1
]}

Pelc, Rebecca S. ^{[2
]}

Muramatsu, Hiromi ^{[1
]}

Andersen, Hanne ^{[3
]}

DeMaso, Christina R. ^{[2
]}

Dowd, Kimberly A. ^{[2
]}

Sutherland, Laura L. ^{[4
]}

Scearce, Richard M. ^{[4
]}

Parks, Robert ^{[4
]}

Wagner, Wendeline ^{[3
]}

Granados, Alex ^{[3
]}

Greenhouse, Jack ^{[3
]}

Walker, Michelle ^{[3
]}

Willis, Elinor

Yu, Jae-Sung ^{[4
]}

McGee, Charles E. ^{[4
]}

Sempowski, Gregory D. ^{[4
]}

Mui, Barbara L. ^{[6
]}

Tam, Ying K. ^{[6
]}

Huang, Yan-Jang ^{[7
,8
]}

Vanlandingham, Dana ^{[7
,8
]}

Holmes, Veronica M. ^{[1
]}

Balachandran, Harikrishnan ^{[9
]}

Sahu, Sujata ^{[9
]}

Lifton, Michelle ^{[9
]}

Higgs, Stephen ^{[7
,8
]}

Hensley, Scott E. ^{[5
]}

Madden, Thomas D. ^{[6
]}

Hope, Michael J. ^{[6
]}

Kariko, Katalin ^{[10
]}

Santra, Sampa ^{[9
]}

Graham, Barney S. ^{[11
]}

Lewis, Mark G. ^{[3
]}

Pierson, Theodore C. ^{[2
]}

Haynes, Barton F. ^{[4
]}

Weissman, Drew ^{[1
]}

机构：

[1] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] Bioqual Inc, Rockville, MD 20850 USA

[4] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA

[5] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Acuitas Therapeut, Vancouver, BC V6T 1Z3, Canada

[7] Kansas State Univ, Coll Vet Med, Diagnost Med & Pathobiol, Manhattan, KS 66506 USA

[8] Kansas State Univ, Biosecur Res Inst, Manhattan, KS 66506 USA

[9] Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[10] BioNTech RNA Pharmaceut, Goldgrube 12, D-55131 Mainz, Germany

[11] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

NATURE | 2017年 / 543卷 / 7644期

关键词：

LIPID NANOPARTICLES; INFECTION; VACCINES; PSEUDOURIDINE; THERAPEUTICS; SPECIFICITY; EXPRESSION; IMMUNITY; VECTORS; THERAPY;

D O I：

10.1038/nature21428

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults(1). 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(2,3). 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 mu g 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 mu g 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.

引用

页码：248 / +

页数：12

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