Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

Wang, Qihui; Yang, Huabing; Liu, Xiaoqing; Dai, Lianpan; Ma, Tian; Qi, Jianxun; Wong, Gary; Peng, Ruchao; Liu, Sheng; Li, Junfu; Li, Shihua; Song, Jian; Liu, Jianying; He, Jianhua; Yuan, Hui; Xiong, Ying; Liao, Yong; Li, Jianhua; Yang, Jianping; Tong, Zhou; Griffin, Bryan D.; Bi, Yang; Liang, Mifang; Xu, Xiao-Ning; Qin, Chuan; Cheng, Gong; Zhang, Xinzheng; Wang, Peiyi; Qiu, Xiangguo; Kobinger, Gary P.; Shi, Yi; Yan, Jinghua; Gao, George F.

doi:10.1126/scitranslmed.aai8336

Cited by 204 publications

(234 citation statements)

References 56 publications

(59 reference statements)

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…Maturation of virus particles occurs during virus egress via the secretory pathway, where furin in the Golgi apparatus cleaves prM, releasing the pr peptide as the virus reaches neutral pH upon exit from the cell (14). The E protein is the major target for neutralizing antibodies, and monoclonal antibodies against all 3 E protein domain (DI, DII, and DIII) target epitopes have been found (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

View full text Add to dashboard Cite

Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (CprM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.KEYWORDS C-prM-E, diagnostics, microneutralization, neutralization, PRNT, reporter, reporter virus particles, vaccine, Zika, prM-E S ince the identification of Zika virus (ZIKV) from a rhesus monkey in Uganda in 1947 (1, 2) until 2010, the virus predominantly circulated between Aedes mosquitoes and nonhuman primates. Periodic episodes were inde...

show abstract

mentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Interestingly, the proportions of ZIKV-specific MAbs in the MAb groups differ. Among the 153 tested MAbs, 63 specifically bind to ZIKV E protein (E MAbs) (8)(9)(10)(11)(12)(13)(14), while 45 of 70 MAbs that convey 50% inhibition of the virus at a concentration of Ͻ1 g/ml are specific to ZIKV (8)(9)(10)(11)(12)(13)(14). The proportion of ZIKV-specific MAbs is further increased in focusing on the MAbs with in vivo protective efficacy.…”

mentioning

confidence: 99%

Monoclonal Antibodies against Zika Virus: Therapeutics and Their Implications for Vaccine Design

Wang

Yan

Gao

2017

J Virol

Self Cite

View full text Add to dashboard Cite

Zika virus (ZIKV) has caused global concern due to its association with neurological complications in newborns and adults. Although no vaccines or antivirals against ZIKV infection have been approved to date, hundreds of monoclonal antibodies (MAbs) have been developed in a short period. Here, we first present a complete picture of the ZIKV MAbs and then focus on the neutralizing mechanisms and immune hot spots uncovered through structural studies, which provide insight for therapeutics and vaccine design.

show abstract

“…Two other monoclonal antibodies showed postexposure protection in mice against Zika virus infection [77]. Isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV has been reported.…”

Section: Antibody-based Therapeuticsmentioning

confidence: 99%

“…Isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV has been reported. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of DENV, the closest relative to ZIKV [77]. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy [77].…”

Section: Antibody-based Therapeuticsmentioning

confidence: 99%