Evidence map›Paper›PMID 17267498›Full record

ArticleJournal of virology2007

Antigenic and immunogenic study of membrane-proximal external region-grafted gp120 antigens by a DNA prime-protein boost immunization strategy.

Mansun Law, Rosa M F Cardoso, Ian A Wilson, Dennis R Burton

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
  2. Review
  3. The wide utility of rabbits as models of human diseases.Experimental & molecular medicine · 2018
    Review
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  16. Neutralizing antibodies to HIV-1 induced by immunization.The Journal of experimental medicine · 2013
    Review
  17. Article
  18. Article
  19. Article
  20. Review
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

4 authors at 1 institution in 1 country.

Mansun LawThe Scripps Research Institute, Department of Immunology (IMM-2), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Rosa M F Cardoso
Ian A Wilson
Dennis R Burton
Scripps Research Institute · US

Funding

HUMAN ANTIBODIES TO HIV-1 BY REPERTOIRE CLONINGR01AI033292 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 1992 to 2013
$5.9M
X-ray structures of HIV-1 neutralizing sitesR01GM046192 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 1991 to 2008
$3.7M
Probing the antibody response to HCV to facilitate rational immunogen designR01AI071084 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2009 to 2013
$3.1M
HUMAN ANTIBODIES TO HIV-1 BY REPERTOIRE CLONINGR37AI033292 · NIAID · SCRIPPS RESEARCH INSTITUTE · PI BURTON, DENNIS R. · 1995 to 2004
$2.4M
NIAID NIH HHS AI-33292NIAID NIH HHS R01 AI033292NIAID NIH HHS R01 AI071084NIAID NIH HHS R37 AI033292NIGMS NIH HHS GM-46192NIGMS NIH HHS R01 GM046192
6 · The paper itself

Abstract

The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of broadly neutralizing monoclonal antibodies (MAbs) 2F5, 4E10, and Z13. Here we engrafted the MPER into the V1/2 region of HIV-1 gp120 to investigate the ability of the engineered antigens to elicit virus-neutralizing antibodies (NAbs). To promote the correct folding and presentation of the helical 4E10 epitope, we flanked the epitope with helical domains and manipulated the helix by sequential deletion of residues preceding the epitope. Binding of the recombinant proteins to MAb 4E10 increased four- to fivefold with the deletion of one or two residues, but it returned to the wild-type level when three residues were deleted, suggesting rotation of the 4E10 epitope along the helix. Immunization of mice and rabbits by electroporation-mediated DNA priming and protein boosting with these constructs elicited high levels of gp120-specific antibodies. A consistent NAb response against the neutralization-resistant, homologous JR-FL virus was detected in rabbits but not in mice. Analysis of the neutralizing activity revealed that the NAbs do not target the MPER or the V1, V2, or V3 region. Through this study, we learned the following. (i) The 4E10 epitope can be manipulated using a "rotate-the-helix" strategy that alters the helix register. However, presentation of this epitope in the immunogenic V1/2 region did not render it immunogenic in mice or rabbits. (ii) DNA vaccination with monomeric gp120-based antigens can elicit a consistent NAb response against the homologous neutralization-resistant virus by targeting epitopes outside the V1, V2, and V3 regions.

Indexed as

AIDS VaccinesAnimalsElectroporationEnzyme-Linked Immunosorbent AssayEpitopesHIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41HumansImmunization, SecondaryMiceMice, Inbred BALB CModels, AnimalNeutralization TestsRabbitsRecombinant Fusion ProteinsAIDS VaccinesEpitopesHIV AntibodiesHIV Envelope Protein gp120HIV Envelope Protein gp41Recombinant Fusion ProteinsVaccines, DNAVaccines, Subunit

Identifiers

PMID17267498
PMCPMC1866136
OpenAlexW2150397848

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.