Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model

被引：87

作者：

Bailey, Mark J. ^{[1
,2
]}

Duehr, James ^{[1
,2
]}

Dulin, Harrison ^{[3
]}

Broecker, Felix ^{[1
]}

Brown, Julia A. ^{[1
,2
]}

Arumemi, Fortuna O. ^{[4
]}

Gonzalez, Maria C. Bermudez ^{[1
,5
]}

Leyva-Grado, Victor H. ^{[1
]}

Evans, Matthew J. ^{[1
]}

Simon, Viviana ^{[1
,5
,6
]}

Lim, Jean K. ^{[1
]}

Krammer, Florian ^{[1
]}

Hai, Rong ^{[3
]}

Palese, Peter ^{[1
,7
]}

Tan, Gene S. ^{[4
,8
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA

[3] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA

[4] J Craig Venter Inst, Infect Dis, La Jolla, CA 92037 USA

[5] Icahn Sch Med Mt Sinai, Global Hlth Emerging Pathogens Inst, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA

[8] Univ Calif San Diego, Dept Med, La Jolla, CA 92037 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

MONOCLONAL-ANTIBODIES; YELLOW-FEVER; NONSTRUCTURAL PROTEIN-1; DENGUE; MICE; INFECTION; ENCEPHALITIS; IMMUNIZATION; REDUCTION; PROSPECTS;

D O I：

10.1038/s41467-018-07008-0

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barre syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage Fc gamma R without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2(-/-) mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen.

引用

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