Evidence map›Paper›PMID 21515681›Full record

ArticleThe Journal of biological chemistry2011

A chimeric HIV-1 envelope glycoprotein trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain induces enhanced antibody and T cell responses.

Thijs van Montfort, Mark Melchers, Gözde Isik, Sergey Menis, Po-Ssu Huang, Katie Matthews, Elizabeth Michael, Ben Berkhout, William R Schief, John P Moore and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

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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

11 authors at 4 institutions in 2 countries.

Thijs van MontfortLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Mark Melchers
Gözde Isik
Sergey Menis
Po-Ssu Huang
Katie Matthews
Elizabeth Michael
Ben Berkhout
William R Schief
John P Moore
Rogier W Sanders
Cornell University · USUniversity of Amsterdam · NLUniversity of Washington · USAcademic Medical Center · NL

Funding

NEUTRALIZATION OF PRIMARY HIV1 VIRUSESR37AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1998 to 2017
$7.0M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
MODIFIED ENVELOPE GLYCOPROTEINS FOR HIV1 VACCINER01AI045463 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1999 to 2010
$4.2M
NIAID NIH HHS AI36082NIAID NIH HHS AI45463NIAID NIH HHS R01 AI036082NIAID NIH HHS R01 AI045463NIAID NIH HHS R37 AI036082
6 · The paper itself

Abstract

An effective HIV-1 vaccine should ideally induce strong humoral and cellular immune responses that provide sterilizing immunity over a prolonged period. Current HIV-1 vaccines have failed in inducing such immunity. The viral envelope glycoprotein complex (Env) can be targeted by neutralizing antibodies to block infection, but several Env properties limit the ability to induce an antibody response of sufficient quantity and quality. We hypothesized that Env immunogenicity could be improved by embedding an immunostimulatory protein domain within its sequence. A stabilized Env trimer was therefore engineered with the granulocyte-macrophage colony-stimulating factor (GM-CSF) inserted into the V1V2 domain of gp120. Probing with neutralizing antibodies showed that both the Env and GM-CSF components of the chimeric protein were folded correctly. Furthermore, the embedded GM-CSF domain was functional as a cytokine in vitro. Mouse immunization studies demonstrated that chimeric Env(GM-CSF) enhanced Env-specific antibody and T cell responses compared with wild-type Env. Collectively, these results show that targeting and activation of immune cells using engineered cytokine domains within the protein can improve the immunogenicity of Env subunit vaccines.

Indexed as

Amino Acid SequenceAnimalsAntibodies, NeutralizingAntibody SpecificityGranulocyte-Macrophage Colony-Stimulating FactorHEK293 CellsHIV-1HIV Envelope Protein gp120HumansMiceModels, MolecularMolecular Sequence DataProtein EngineeringProtein MultimerizationProtein Structure, QuaternaryProtein Structure, TertiaryAntibodies, Neutralizinggp120 protein, Human immunodeficiency virus 1Granulocyte-Macrophage Colony-Stimulating FactorHIV Envelope Protein gp120Recombinant Fusion ProteinsViral Vaccines

Identifiers

PMID21515681
PMCPMC3121371
OpenAlexW2160715721

What OpenQuestion holds

Textmetadata
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.