Delineating antibody recognition against Zika virus during natural infection

Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that shares a considerable degree of homology with dengue virus (DENV). Here, we examined longitudinal antibody response against ZIKV during natural infection in 2 convalescent individuals. By decomposing the antibody recognition into DI/DII and DIII of the E glycoprotein, we showed their development in humans followed a spatiotemporal hierarchy. Plasma binding to DI/DII appeared to peak and wane during early infection with extensive cross-reactivity with DI/DII of DENV. Binding to DIII, however, peaked early but persisted months into the infection without detectable cross-reactivity with DIII of DENV. A clear trend of increase in DIII-specific neutralizing activity was observed over the course of infection. mAbs isolated during early infection are largely DI/DII specific, weakly neutralizing, and highly cross-reactive with DENV, while those from later infection are more diverse in recognition, potently neutralizing, and ZIKV specific. The most potent neutralizing mAb targeting the DIII provided 100% protection in mice from lethal ZIKV infection and could therefore serve as a promising candidate for antibody-based therapy and prevention. The dynamic features unveiled here will assist us to better understand the pathogenesis of ZIKV infection and inform rational design of vaccines.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:2

Enthalten in:

JCI insight - 2(2017), 12 vom: 15. Juni

Sprache:

Englisch

Beteiligte Personen:

Yu, Lei [VerfasserIn]
Wang, Ruoke [VerfasserIn]
Gao, Fei [VerfasserIn]
Li, Min [VerfasserIn]
Liu, Jianying [VerfasserIn]
Wang, Jian [VerfasserIn]
Hong, Wenxin [VerfasserIn]
Zhao, Lingzhai [VerfasserIn]
Wen, Yingfen [VerfasserIn]
Yin, Chibiao [VerfasserIn]
Wang, Hua [VerfasserIn]
Zhang, Qi [VerfasserIn]
Li, Yangyang [VerfasserIn]
Zhou, Panpan [VerfasserIn]
Zhang, Rudian [VerfasserIn]
Liu, Yang [VerfasserIn]
Tang, Xiaoping [VerfasserIn]
Guan, Yongjun [VerfasserIn]
Qin, Cheng-Feng [VerfasserIn]
Chen, Ling [VerfasserIn]
Shi, Xuanling [VerfasserIn]
Jin, Xia [VerfasserIn]
Cheng, Gong [VerfasserIn]
Zhang, Fuchun [VerfasserIn]
Zhang, Linqi [VerfasserIn]

Links:

Volltext

Themen:

Immunology
Infectious disease
Journal Article

Anmerkungen:

Date Revised 20.11.2019

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1172/jci.insight.93042

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM272934895