ArticleJournal of acquired immune deficiency syndromes (1999)2014
Rational design and characterization of the novel, broad and potent bispecific HIV-1 neutralizing antibody iMabm36.
Article in Journal of acquired immune deficiency syndromes (1999), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Exceptionally broad HIV-1 neutralization via bispecific antibody-mediated prepositioning.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A broad antibody with enhanced HIV-1 neutralization via bispecific antibody-mediated prepositioning.Nature communications · 2025Article
- Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals.Nature communications · 2023Article
- Design of a Bispecific HIV Entry Inhibitor Targeting the Cell Receptor CD4 and Viral Fusion Protein Gp41.Frontiers in cellular and infection microbiology · 2022Article
- Review
- Syntheses and anti-HIV and human cluster of differentiation 4 (CD4) down-modulating potencies of pyridine-fused cyclotriazadisulfonamide (CADA) compounds.Bioorganic & medicinal chemistry · 2020Article
- An Inside Job: Applications of Intracellular Single Domain Antibodies.Biomolecules · 2020Review
- Engineering and characterising a novel, highly potent bispecific antibody iMab-CAP256 that targets HIV-1.Retrovirology · 2019Article
- eCD4-Ig Limits HIV-1 Escape More Effectively than CD4-Ig or a Broadly Neutralizing Antibody.Journal of virology · 2019Article
- Neutralizing antibodies for HIV-1 prevention.Current opinion in HIV and AIDS · 2019Review
- Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection.Antimicrobial agents and chemotherapy · 2019Review
- Novel vaccines: Technology and development.The Journal of allergy and clinical immunology · 2019Review
- Single-Domain Antibodies and Their Formatting to Combat Viral Infections.Antibodies (Basel, Switzerland) · 2018Review
- HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins.Molecular therapy. Nucleic acids · 2018Review
- Targeting the HIV-1 Spike and Coreceptor with Bi- and Trispecific Antibodies for Single-Component Broad Inhibition of Entry.Journal of virology · 2018Article
- Engineering multi-specific antibodies against HIV-1.Retrovirology · 2018Review
- Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice.The Journal of clinical investigation · 2018Article
- Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections.PLoS pathogens · 2018Article
- Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity.Nature communications · 2018Article
- Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundAlthough broadly neutralizing monoclonal antibodies (bNAbs) have always been considered to be a potential therapeutic option for the prophylaxis and treatment of HIV infection, their lack of breadth against all HIV variants has been one of the limiting factors. To provide sufficient neutralization breadth and potency against diverse viruses, including neutralization escape mutants, strategies to combine different bNAbs have been explored recently.
methodsWe rationally designed and engineered a novel bispecific HIV-1-neutralizing antibody (bibNAb), iMabm36. The potency and breadth of iMabm36 against HIV were extensively characterized in vitro.
resultsiMabm36 comprises the anti-CD4 Ab ibalizumab (iMab) linked to 2 copies of the single-domain Ab m36, which targets a highly conserved CD4-induced epitope. iMabm36 neutralizes a majority of a large, multiclade panel of pseudoviruses (96%, n = 118) at an IC50 concentration of less than 10 µg/mL, with 83% neutralized at an IC50 concentration of less than 0.1 µg/mL. In addition, iMabm36 neutralizes a small panel of replication-competent transmitted-founder viruses to 100% inhibition at a concentration of less than 0.1 µg/mL in a peripheral blood mononuclear cell-based neutralizing assay. Mechanistically, the improved antiviral activity of iMabm36 is dependent on both the CD4-binding activity of the iMab component and the CD4i-binding activity of the m36 component. After characterizing that viral resistance to iMabm36 neutralization was due to mutations residing in the bridging sheet of gp120, an optimized m36 variant was engineered that, when fused to iMab, improved antiviral activity significantly.
conclusionsThe interdependency of this dual mechanism of action enables iMabm36 to potently inhibit HIV-1 entry. These results demonstrate that mechanistic-based design of bibNAbs can generate potential preventive and therapeutic candidates for HIV/AIDS.
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