Evidence map›Paper›PMID 31189716›Full record

ArticleJournal of virology2019

Rational Design of Zika Virus Subunit Vaccine with Enhanced Efficacy.

Wanbo Tai, Jiawei Chen, Guangyu Zhao, Qibin Geng, Lei He, Yuehong Chen, Yusen Zhou, Fang Li, Lanying Du

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 47 citations in OpenAlex.

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  12. Widespread amyloid aggregates formation by Zika virus proteins and peptides.Protein science : a publication of the Protein Society · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Wanbo Tai *New York Blood Center, Lindsley F. Kimball Research Institute, New York, New York, USA.
Jiawei Chen *New York Blood Center, Lindsley F. Kimball Research Institute, New York, New York, USA.
Guangyu ZhaoState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Qibin GengDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.
Lei HeState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Yuehong ChenState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Yusen Zhou *State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Fang Li *Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA lifang@umn.edu ldu@nybc.org.
Lanying Du *New York Blood Center, Lindsley F. Kimball Research Institute, New York, New York, USA lifang@umn.edu ldu@nybc.org.
Institute of Microbiology · CNNew York Blood Center · USUniversity of Minnesota · USZhengzhou University · CN

Funding

Structure-based design of coronavirus subunit vaccinesR01AI139092 · NIAID · NEW YORK BLOOD CENTER · PI DU, LANYING · 2018 to 2022
$4.2M
A novel and effective nanobody to prevent and treat Zika virus infectionR21AI137790 · NIAID · NEW YORK BLOOD CENTER · PI DU, LANYING · 2019 to 2020
$490k
NIAID NIH HHS R01 AI139092NIAID NIH HHS R21 AI137790
6 · The paper itself

Abstract

Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice.

Indexed as

AnimalsAntibodies, NeutralizingAntibodies, ViralDisease Models, AnimalEpitopesFemaleHumansMiceNeutralization TestsPregnancyProtein DomainsVaccines, SubunitViral Envelope ProteinsViral VaccinesZika VirusZika Virus InfectionAntibodies, NeutralizingAntibodies, ViralEpitopesVaccines, SubunitViral Envelope ProteinsViral Vaccinesdomain IIIenvelope proteinepitope shieldingglycan probeintrinsic limitation of subunit vaccine designsvaccine efficacyZika virus

Identifiers

PMID31189716
PMCPMC6694833
OpenAlexW2950833983

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.