Evidence map›Paper›PMID 26962221›Full record

ArticleJournal of virology2016

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds.

Navid Madani, Amy M Princiotto, David Easterhoff, Todd Bradley, Kan Luo, Wilton B Williams, Hua-Xin Liao, M Anthony Moody, Ganesh E Phad, Néstor Vázquez Bernat and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

32 citing papers in PubMed, 41 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

16 authors at 6 institutions in 2 countries.

Navid MadaniDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Amy M PrinciottoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
David EasterhoffDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Todd BradleyDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Kan LuoDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Wilton B WilliamsDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Hua-Xin LiaoDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
M Anthony MoodyDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Ganesh E PhadDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Néstor Vázquez BernatDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Bruno MelilloDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sampa SantraCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Amos B SmithDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Gunilla B Karlsson HedestamDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Barton HaynesDuke Human Vaccine Institute, Department of Medicine, and Department of Immunology, Duke University Medical Center, Durham, NC, USA.
Joseph SodroskiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA joseph_sodroski@dfci.harvard.edu.
Duke Medical Center · USKarolinska Institutet · SEDana-Farber Cancer Institute · USUniversity of Pennsylvania · USBeth Israel Deaconess Medical Center · USHarvard University · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI MCMICHAEL, ANDREW JAMES · 2012 to 2018
$204.7M
Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2M
HIV-1 ENVELOPE GLYCOPROTEINSR37AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1996 to 2015
$11.6M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Conformational Landscape of the HIV-1 Envelope GlycoproteinsR01AI124982 · NIAID · DANA-FARBER CANCER INST · PI SODROSKI, JOSEPH G · 2016 to 2025
$6.7M
Design of dendrimeric HIV-1 transmission inhibitors targeting gp120 Phe-43 cavityR56AI090682 · NIAID · DANA-FARBER CANCER INST · PI MADANI, NAVID · 2010 to 2010
$576k
NIAID NIH HHS R01 AI124982NIAID NIH HHS R37 AI024755NIAID NIH HHS R56 AI090682NIAID NIH HHS UM1 AI100645NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

unlabelledThe human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recognize conserved Env epitopes are thought to be an important component of a protective immune response. However, to date, HIV-1 Env immunogens that elicit broadly neutralizing antibodies have not been identified, creating hurdles for vaccine development. Small-molecule CD4-mimetic compounds engage the CD4-binding pocket on the gp120 exterior Env and induce Env conformations that are highly sensitive to neutralization by antibodies, including antibodies directed against the conserved Env region that interacts with CCR5/CXCR4. Here, we show that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within 6 months by several Env vaccine candidates, including gp120 monomers. Monoclonal antibodies directed against the gp120 V2 and V3 variable regions were isolated from the immunized monkeys and humans; these monoclonal antibodies neutralized a primary HIV-1 only when the virus was sensitized by a CD4-mimetic compound. Thus, in addition to their direct antiviral effect, CD4-mimetic compounds dramatically enhance the HIV-1-neutralizing activity of antibodies that can be elicited with currently available immunogens. Used as components of microbicides, the CD4-mimetic compounds might increase the protective efficacy of HIV-1 vaccines. IMPORTANCE: Preventing HIV-1 transmission is a high priority for global health. Eliciting antibodies that can neutralize transmitted strains of HIV-1 is difficult, creating problems for the development of an effective vaccine. We found that small-molecule CD4-mimetic compounds sensitize HIV-1 to antibodies that can be elicited in vaccinated humans and monkeys. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAnti-HIV AgentsCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHaplorhiniHIV-1HIV AntibodiesHIV Envelope Protein gp120HIV InfectionsHumansImmunizationMolecular MimicryPeptide FragmentsAntibodies, MonoclonalAntibodies, NeutralizingAnti-HIV AgentsCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Envelope Protein gp120HIV envelope protein gp120 (305-321)Peptide Fragments

Identifiers

PMID26962221
PMCPMC4859707
OpenAlexW2293045910

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.