Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

被引：218

作者：

Richner, Justin M. ^{[1
,18
]}

Jagger, Brett W. ^{[1
,18
]}

Shan, Chao ^{[2
,18
]}

Fontes, Camila R. ^{[2
,18
]}

Dowd, Kimberly A. ^{[3
,18
]}

Cao, Bin ^{[4
]}

Himansu, Sunny ^{[5
]}

Caine, Elizabeth A. ^{[1
]}

Nunes, Bruno T. D. ^{[2
,6
]}

Medeiros, Daniele B. A. ^{[2
,6
]}

Muruato, Antonio E. ^{[2
,7
]}

Foreman, Bryant M. ^{[3
]}

Luo, Huanle ^{[7
]}

Wang, Tian ^{[8
,11
]}

Barrett, Alan D. ^{[11
]}

Weaver, Scott C. ^{[8
,10
,11
]}

Vasconcelos, Pedro F. C. ^{[6
,15
]}

Rossi, Shannan L. ^{[7
,10
]}

Ciaramella, Giuseppe ^{[5
]}

Mysorekar, Indira U. ^{[4
,12
]}

Pierson, Theodore C. ^{[3
]}

Shi, Pei-Yong ^{[2
,9
,10
,16
,17
]}

Diamond, Michael S. ^{[1
,12
,13
,14
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, St Louis, MO USA

[2] Univ Texas Med Branch, Dept Biochem Mol Biol, Galveston, TX USA

[3] Natl Inst Hlth, Viral Pathogenesis Sect, Lab Viral Dis, Bethesda, MD USA

[4] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO USA

[5] Valera LLC, Moderna Venture, 500 Technol Sq, Cambridge, MA USA

[6] Evandro Chagas Inst, Dept Arbovirol & Hemorrhag Fevers, Minist Hlth, Ananindeua, Para, Brazil

[7] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA

[8] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA

[9] Univ Texas Med Branch, Inst Translat Sci, Galveston, TX USA

[10] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX USA

[11] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX USA

[12] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[13] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO USA

[14] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, St Louis, MO USA

[15] Para State Univ, Dept Pathol, Belem, Para, Brazil

[16] Univ Texas Med Branch, Dept Pharmacol Toxicol, Galveston, TX USA

[17] Univ Texas Med Branch, Sealy Ctr Struct Biol Mol Biophys, Galveston, TX USA

[18] IIT Res Inst, Chicago, IL USA

来源：

CELL | 2017年 / 170卷 / 02期

关键词：

MESSENGER-RNA VACCINES; N-LINKED GLYCOSYLATION; WEST NILE VIRUS; NS1; PROTEIN; DENGUE VIRUS; CDNA CLONE; MOUSE; ANTIBODIES; ORGANIZATION; REPLICATION;

D O I：

10.1016/j.cell.2017.06.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.

引用

页码：273 / +

页数：23

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