ArticleJournal of pharmaceutical sciences2020
Framework Mutations of the 10-1074 bnAb Increase Conformational Stability, Manufacturability, and Stability While Preserving Full Neutralization Activity.
Article in Journal of pharmaceutical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed.
- Beyond counting: how single-cell long-read sequencing turns transcriptome complexity into precision targets.Frontiers in oncology · 2026Review
- Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.Current HIV research · 2026Review
- Engineering HIV antibodies with enhanced breadth and potency of neutralization through multistate affinity maturation.bioRxiv : the preprint server for biology · 2025Article
- A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.Structure (London, England : 1993) · 2025Article
- AI-based antibody discovery platform identifies novel, diverse, and pharmacologically active therapeutic antibodies against multiple SARS-CoV-2 strains.Antibody therapeutics · 2024Article
- Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.Clinical microbiology reviews · 2024Review
- A candidate antibody drug for prevention of malaria.Nature medicine · 2024Article
- Recent Advances and Future Directions in Downstream Processing of Therapeutic Antibodies.International journal of molecular sciences · 2022Review
- Expanding the toolbox for predictive parameters describing antibody stability considering thermodynamic and kinetic determinants.Pharmaceutical research · 2021Article
- Broadly Neutralizing Antibodies for HIV-1 Prevention.Frontiers in immunology · 2021Review
- Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV.Current opinion in HIV and AIDS · 2020Review
- The Emergency Response Capacity of Plant-Based Biopharmaceutical Manufacturing-What It Is and What It Could Be.Frontiers in plant science · 2020Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The broadly neutralizing anti-HIV antibody, 10-1074, is a highly somatically hypermutated IgG1 being developed for prophylaxis in sub-Saharan Africa. A series of algorithms were applied to identify potentially destabilizing residues in the framework of the Fv region. Of 17 residues defined, a variant was identified encompassing 1 light and 3 heavy chain residues, with significantly increased conformational stability while maintaining full neutralization activity. Central to the stabilization was the replacement of the heavy chain residue T108 with R108 at the base of the CDR3 loop which allowed for the formation of a nascent salt bridge with heavy chain residue D137. Three additional mutations were necessary to confer increased conformational stability as evidenced by differential scanning fluorimetry and isothermal chemical unfolding. In addition, we observed increased stability during low pH incubation in which 40% of the parental monomer aggregated while the combinatorial variant showed no increase in aggregation. Incubation of the variant at 100 mg/mL for 6 weeks at 40°C showed a 9-fold decrease in subvisible particles ≥2 μm relative to the parental molecule. Stability-based designs have also translated to improved pharmacokinetics. Together, these data show that increasing conformational stability of the Fab can have profound effects on the manufacturability and long-term stability of a monoclonal antibody.
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