Evidence map›Paper›PMID 36729903›Full record

ArticlemAbs

Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency.

Baoshan Zhang, Jason Gorman, Young D Kwon, Amarendra Pegu, Cara W Chao, Tracy Liu, Mangaiarkarasi Asokan, Michael F Bender, Tatsiana Bylund, Leland Damron and 18 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06585891 (VRC 617), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 8% 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.

NCT06585891 phase1completednot on this map

VRC 617: A Phase 1, Open-Label, Dose-Escalation Study to Evaluate Safety and Pharmacokinetics of a Human Bispecific Antibody, VRC-HIVMAB0121-00-AB (CAP256J3LS) Administered Intravenously or Subcutaneously to Healthy Adults

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2024 to 2025Enrolled24ConditionsHIV InfectionArmsVRC-HIVMAB0121-00-AB
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  9. Review
  10. Article
  11. Review
  12. The potential of monoclonal antibodies for colorectal cancer therapy.Medical oncology (Northwood, London, England) · 2023
    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

28 authors at 4 institutions in 1 country.

Baoshan ZhangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Jason GormanVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Young D KwonVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Amarendra PeguVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Cara W ChaoVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Tracy LiuVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Mangaiarkarasi AsokanVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Michael F BenderVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Tatsiana BylundVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Leland DamronVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Deepika GollapudiVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Paula LeiVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Yile LiVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Cuiping LiuVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Mark K LouderVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Krisha McKeeVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Adam S OliaVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Reda RawiVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Arne SchönDepartment of Biology, Johns Hopkins University, Baltimore, MD, USA.
Shuishu WangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Eun Sung YangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Yongping YangVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Kevin CarltonVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Nicole A Doria-RoseVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Lawrence ShapiroDepartment of Biochemistry, Columbia University, New York, NY, USA.
Michael S SeamanBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
John R MascolaVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.
Peter D KwongVaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-3560-232X
National Institutes of Health · USBeth Israel Deaconess Medical Center · USColumbia University · USJohns Hopkins University · US

Funding

Neutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6M
TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
Computational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1M
Intramural NIH HHS ZIA AI005022NIGMS NIH HHS P41 GM103310
6 · The paper itself

Abstract

Antibody CAP256-VRC26.25 targets the second hypervariable region (V2) at the apex of the HIV envelope (Env) trimer with extraordinary neutralization potency, although less than optimal breadth. To improve breadth, we linked the light chain of CAP256V2LS, an optimized version of CAP256-VRC26.25 currently under clinical evaluation, to the llama nanobody J3, which has broad CD4-binding site-directed neutralization. The J3-linked bispecific antibody exhibited improved breadth and potency over both J3 and CAP256V2LS, indicative of synergistic neutralization. The cryo-EM structure of the bispecific antibody in complex with a prefusion-closed Env trimer revealed simultaneous binding of J3 and CAP256V2LS. We further optimized the pharmacokinetics of the bispecific antibody by reducing the net positive charge of J3. The optimized bispecific antibody, which we named CAP256.J3LS, had a half-life similar to CAP256V2LS in human FcRn knock-in mice and exhibited suitable auto-reactivity, manufacturability, and biophysical risk. CAP256.J3LS neutralized over 97% of a multiclade 208-strain panel (geometric mean concentration for 80% inhibition (IC

Indexed as

Antibodies, BispecificHIV-1HIV InfectionsAnimalsAntibodies, NeutralizingBinding SitesHIV AntibodiesHumansMiceNeutralization TestsAntibodies, BispecificAntibodies, NeutralizingHIV AntibodiesAntibody half-lifeantibody improvementbispecific antibodyCAP256-VRC26.25CD4-binding sitecryo-electron microscopyHIV-1J3 nanobodyV2 apex

Identifiers

PMID36729903
PMCPMC9897750
OpenAlexW4318914677

What OpenQuestion holds

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Registered trials

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.