Evidence map›Paper›PMID 29593050›Full record

ArticleJournal of virology2018

eCD4-Ig Variants That More Potently Neutralize HIV-1.

Ina Fetzer, Matthew R Gardner, Meredith E Davis-Gardner, Neha R Prasad, Barnett Alfant, Jesse A Weber, Michael Farzan

Abstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
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

23 citing papers in PubMed.

  1. Article
  2. Article
  3. SHIV fights back to evade destruction by eCD4-Ig but not without suffering debilitating wounds.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  4. In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Research square · 2024
    Article
  9. Human gene therapy · 2022
    Article
  10. Article
  11. Broadly neutralizing monoclonal antibodies for HIV prevention.Journal of the International AIDS Society · 2021
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

7 authors.

Ina FetzerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Matthew R GardnerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Meredith E Davis-GardnerDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Neha R PrasadDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Barnett AlfantDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Jesse A WeberDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
Michael FarzanDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA mfarzan@scripps.edu.

Funding

Cell and Gene Therapy for HIV CureUM1AI126623 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R, KIEM, HANS-PETER · 2016 to 2020
$24.2M
Viral escape from AAV expressed transgenesP01AI100263 · NIAID · SCRIPPS FLORIDA · PI GAO, GUANGPING · 2012 to 2016
$11.9M
Therapeutic Use of an Enhanced Form of CD4-IgR37AI091476 · NIAID · UNIVERSITY OF FLORIDA · PI FARZAN, MICHAEL R. · 2016 to 2025
$9.2M
Optimizing eCD4-Ig for eradication and a functional cureR01AI129868 · NIAID · UNIVERSITY OF FLORIDA · PI FARZAN, MICHAEL R. · 2017 to 2021
$5.2M
An AAV Approach to Treating HIVF32AI122980 · NIAID · SCRIPPS FLORIDA · PI GARDNER, MATTHEW RYAN · 2016 to 2017
$116k
NIAID NIH HHS F32 AI122980NIAID NIH HHS P01 AI100263NIAID NIH HHS R01 AI129868NIAID NIH HHS R37 AI091476NIAID NIH HHS UM1 AI126623
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralized all HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates that it has been tested against, suggesting that it may be useful in clinical settings, where antibody escape is a concern. Here, we characterize three new eCD4-Ig variants, each with a different architecture and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as the original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented the promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications.

Indexed as

AnimalsAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityCD4 AntigensCD4 ImmunoadhesinsCD4-Positive T-LymphocytesCell LineDogsHEK293 CellsHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansImmunologic FactorsRecombinant Fusion ProteinsAntibodies, NeutralizingCD4 AntigensCD4 ImmunoadhesinsHIV AntibodiesHIV Envelope Protein gp120Immunologic FactorsRecombinant Fusion ProteinsCD4CD4-IgcoreceptoreCD4-Ighuman immunodeficiency virus

Identifiers

PMID29593050
PMCPMC5974481

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Registered trials

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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.