ArticleScientific reports2022
Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in HIV-uninfected women.Nature communications · 2025Trial
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.PLoS pathogens · 2026Article
- Translational insights into manufacturability and stability of broadly neutralizing antibodies for pediatric HIV prevention: lessons from plant-produced CAP256-VRC26.25.Frontiers in pediatrics · 2026Article
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.bioRxiv : the preprint server for biology · 2025Article
- Rapid loss of activity but not serum concentration in a passive infusion clinical trial of an HIV neutralizing antibody.medRxiv : the preprint server for health sciences · 2025Article
- Safety and pharmacokinetics of N6LS, a broadly neutralising monoclonal antibody for HIV: a phase 1, open-label, dose-escalation study in healthy adults.The lancet. HIV · 2025Article
- Multilayered HIV-1 resistance in HSPCs through CCR5 Knockout and B cell secretion of HIV-inhibiting antibodies.Nature communications · 2025Article
- Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage.Cell reports · 2025Article
- Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025.Pathogens & immunity · 2025Article
- Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS.JCI insight · 2024Article
- Article
- Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency.mAbsArticle
Corrections and comments
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Authors and funding
28 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.
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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.