Evidence map›Paper›PMID 22142583›Full record

ArticleVaccine2012

An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site.

Fatima K Ahmed, Brenda E Clark, Dennis R Burton, Ralph Pantophlet

Abstract read
In one paragraph

Article in Vaccine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  7. Saponins fromMolecules (Basel, Switzerland) · 2019
    Review
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  15. Review
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  17. Review
  18. Neutralizing antibodies to HIV-1 induced by immunization.The Journal of experimental medicine · 2013
    Review
  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 2 institutions in 2 countries.

Fatima K AhmedDepartment of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A1S6, Canada.
Brenda E Clark
Dennis R Burton
Ralph Pantophlet
Simon Fraser University · CAScripps 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
HUMAN ANTIBODIES TO HIV-1 BY REPERTOIRE CLONINGR37AI033292 · NIAID · SCRIPPS RESEARCH INSTITUTE · PI BURTON, DENNIS R. · 1995 to 2004
$2.4M
IMMUNOFOCUSING TO A NEUTRALIZING EPITOPE ON GP120R01AI060425 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2004 to 2007
$1.8M
CIHR 200100NIAID NIH HHS AI33292NIAID NIH HHS AI60425NIAID NIH HHS R01 AI033292NIAID NIH HHS R01 AI060425NIAID NIH HHS R37 AI033292
6 · The paper itself

Abstract

A major priority in HIV vaccine research is the development of an immunogen to elicit broadly neutralizing antibodies (NAbs). Monoclonal antibody (mAb) b12 is one of now several broadly neutralizing mAbs that bind epitopes overlapping the CD4-binding site (CD4bs) on HIV-1 gp120 and that serve as templates to engineer effective immunogens. We are exploring a strategy whereby extra glycans are incorporated onto gp120 to occlude the epitopes of non-neutralizing mAbs while maintaining exposure of the b12 site. Immunizing with these so-called hyperglycosylated gp120s is hypothesized to preferentially elicit b12-like NAbs. Here, the effects of two adjuvants, monophosphoryl lipid A (MPL) and Quil A, on eliciting b12-like responses when formulated with a new hyperglycosylated mutant, ΔN2mCHO(Q105N), is presented. Sera from ΔN2mCHO(Q105N)_MPL immunized animals bound the homologous antigen ΔN2mCHO(Q105N) with greater preference than sera from ΔN2mCHO(Q105N)_QuilA immunized animals, demonstrating the modulation of antibody fine specificity by these two adjuvants. We also found that sera from ΔN2mCHO(Q105N)_QuilA immunized animals bound best to a resurfaced HIV gp120 core protein on which non-CD4bs epitopes are substituted with non-HIV residues, suggesting that these sera contain a relatively larger fraction of CD4bs-specific antibodies. Consistent with these data, inhibition assays revealed epitope overlap with the binding sites of the CD4bs-specific antibodies b12, b13 and VRC03. Unexpectedly, these sera did not exhibit significant neutralizing activity against a set of HIV-1 primary strains. Our results show that although formulating mutant ΔN2mCHO(Q105N) with Quil A promotes the elicitation of CD4bs-directed antibodies relative to wild-type gp120, tweaking of the immunization regimen is needed to yield robust, CD4bs-focused NAbs.

Indexed as

Adjuvants, ImmunologicAIDS VaccinesAnimalsAntibodies, NeutralizingBinding SitesFemaleHIV AntibodiesHIV Envelope Protein gp120Lipid AMiceMice, Inbred BALB CNeutralization TestsQuillaja SaponinsSaponinsVaccines, SyntheticAdjuvants, ImmunologicAIDS VaccinesAntibodies, Neutralizinggp120 protein, Human immunodeficiency virus 1HIV AntibodiesHIV Envelope Protein gp120Lipid Amonophosphoryl lipid AQuil AQuillaja SaponinsSaponinsVaccines, Synthetic

Identifiers

PMID22142583
PMCPMC3733221
OpenAlexW2025915045

What OpenQuestion holds

Textmetadata
LicenceTDM
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.