ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Anti-drug Antibody Responses Impair Prophylaxis Mediated by AAV-Delivered HIV-1 Broadly Neutralizing Antibodies.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Employing Broadly Neutralizing Antibodies as a Human Immunodeficiency Virus Prophylactic & Therapeutic Application.Frontiers in immunology · 2021Pooled it
- Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.Vaccines · 2026Review
- Review
- Overcoming host immune responses to an AAV-delivered HIV-1 bNAb in rhesus macaques mediated by co-delivery of PD-L1.bioRxiv : the preprint server for biology · 2026Article
- Co-delivered PD-L1 rescues the protective efficacy mediated by an AAV-expressed HIV-1 bNAb.bioRxiv : the preprint server for biology · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Article
- The Immunogenicity of AAV-Encoded HIV-1 bNAbs in Rhesus Macaques Is Unaffected by a Short Course of the Immunomodulator CTLA4Ig.AIDS research and human retroviruses · 2025Article
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Article
- Review
- Multilayered HIV-1 resistance in HSPCs through CCR5 Knockout and B cell secretion of HIV-inhibiting antibodies.Nature communications · 2025Article
- Anti-Drug Antibody Response to Therapeutic Antibodies and Potential Mitigation Strategies.Biomedicines · 2025Review
- In pursuit of an HIV cure: from stem cell transplants to gene therapies.Frontiers in genome editing · 2025Review
- Adeno-associated virus mediated expression of monoclonal antibody MR191 protects mice against Marburg virus and provides long-term expression in sheep.Gene therapy · 2025Article
- Reprogramming human B cells with custom heavy-chain antibodies.Nature biomedical engineering · 2024Article
- Influence of AAV vector tropism on long-term expression and Fc-γ receptor binding of an antibody targeting SARS-CoV-2.Communications biology · 2024Article
- In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.Nature biomedical engineering · 2024Article
- Broadly neutralizing antibodies targeting HIV: Progress and challenges.Clinical immunology (Orlando, Fla.) · 2023Review
- Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly compare the performance of the IgG1-Fc and the IgG2-Fc domains in a prophylactic setting, we compared AAV1 expression of rhesus IgG1 and IgG2 forms of four anti-HIV bNAbs: 3BNC117, NIH45-46, 10-1074, and PGT121. Interestingly, IgG2-isotyped bNAbs elicited significantly lower ADA than their IgG1 counterparts. We also observed significant protection from two SHIV-AD8 challenges in macaques expressing IgG2-isotyped bNAbs, but not from those expressing IgG1. Our data suggest that monoclonal antibodies isotyped with IgG2-Fc domains are less immunogenic than their IgG1 counterparts, and they highlight ADAs as a key barrier to the use of AAV1-expressed bNAbs.
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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.