Evidence map›Paper›PMID 31544770›Full record

ArticleEBioMedicine2019

Proteins mimicking epitope of HIV-1 virus neutralizing antibody induce virus-neutralizing sera in mice.

Petr Kosztyu, Milan Kuchar, Jiri Cerny, Lucia Barkocziova, Michal Maly, Hana Petrokova, Lydie Czernekova, Veronika Liskova, Leona Raskova Kafkova, Pavlina Knotigova and 4 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Petr KosztyuDepartment of Immunology, Palacky University in Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic.
Milan KucharLaboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Jiri CernyLaboratory of Structural Bioinformatics of Proteins, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Lucia BarkocziovaDepartment of Immunology, Palacky University in Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic.
Michal MalyLaboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Hana PetrokovaLaboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Lydie CzernekovaDepartment of Immunology, Palacky University in Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic.
Veronika LiskovaLaboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic.
Leona Raskova KafkovaDepartment of Immunology, Palacky University in Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic.
Pavlina KnotigovaDepartment of Pharmacology and Immunotherapy, Veterinary Research Institute, Hudcova 70, Brno 621 00, Czech Republic.
Josef MasekDepartment of Pharmacology and Immunotherapy, Veterinary Research Institute, Hudcova 70, Brno 621 00, Czech Republic.
Jaroslav TuranekDepartment of Pharmacology and Immunotherapy, Veterinary Research Institute, Hudcova 70, Brno 621 00, Czech Republic. Electronic address: turanek@vri.cz.
Petr MalyLaboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV Research Center, Prumyslova 595, Vestec 252 50, Czech Republic. Electronic address: petr.maly@ibt.cas.cz.
Milan RaskaDepartment of Immunology, Palacky University in Olomouc, Hnevotinska 3, Olomouc 779 00, Czech Republic; Department of Pharmacology and Immunotherapy, Veterinary Research Institute, Hudcova 70, Brno 621 00, Czech Republic. Electronic address: milan.raska@upol.cz.
Czech Academy of Sciences, Institute of Biotechnology · CZPalacký University Olomouc · CZVeterinary Research Institute · CZCzech Academy of Sciences · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to the discovery of broadly neutralizing antibodies.

methodsWe employed a highly complex combinatorial protein library derived from a 5 kDa albumin-binding domain scaffold, fused with support protein of total 38 kDa, to screen for binders of broadly neutralizing antibody VRC01 paratope. The most specific binders were used for immunization of experimental mice to elicit Env-specific antibodies and to test their neutralization activity using a panel of HIV-1 clade C and B pseudoviruses.

findingsThree most specific binders designated as VRA017, VRA019, and VRA177 exhibited high specificity to VRC01 antibody. Immunized mice produced Env-binding antibodies which neutralize eight of twelve HIV-1 Tier 2 pseudoviruses. Molecular modelling revealed a shape complementarity between VRA proteins and a part of VRC01 gp120 interacting surface.

interpretationThis strategy based on the identification of protein replicas of broadly neutralizing antibody paratope represents a novel approach in HIV-1 vaccine development. This approach is not affected by low immunogenicity of neutralization-sensitive epitopes, variability, and unique biochemical properties of HIV-1 Env used as a crucial antigen in the majority of contemporary tested vaccines. FUND: Czech Health Research Council 15-32198A, Ministry of Health, Czech Republic.

Indexed as

AIDS VaccinesAmino Acid SequenceAnimalsAntibodies, NeutralizingAntigens, ViralDisease Models, AnimalEpitopesHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansImmunoglobulin GMiceModels, MolecularProtein ConformationAIDS VaccinesAntibodies, NeutralizingAntigens, ViralEpitopesHIV AntibodiesHIV Envelope Protein gp120Immunoglobulin GAlbumin-binding domain scaffoldAntibody paratope mimeticsCombinatorial protein libraryHIV-1 vaccineNeutralizing antibodyProtein docking

Identifiers

PMID31544770
PMCPMC6796546
OpenAlexW2973849421

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.