ArticleNature2015
AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 2 of them syntheses that pooled it.
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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
204 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A potential antibody repertoire diversification mechanism through tyrosine sulfation for biotherapeutics engineering and production.Frontiers in immunology · 2022Pooled it
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.Molecular therapy. Advances · 2026Article
- Durable antiviral protection via directMolecular therapy. Advances · 2026Article
- Engineering Protein-Based HIV Entry Inhibitors: Advances, Challenges, and Translational Strategies.Biomolecules · 2026Review
- Co-delivered PD-L1 rescues the protective efficacy mediated by an AAV-expressed HIV-1 bNAb.bioRxiv : the preprint server for biology · 2026Article
- 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
- Engineering B cells to express fully customizable antibodies with enhanced Fc functions.Nature communications · 2026Article
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.The Journal of clinical investigation · 2026Article
- Article
- HIV broadly neutralizing antibody escape dynamics drive the outcome of AAV-vectored immunotherapy in humanized mice.Immunity · 2026Article
- B Cell Receptor's function in virus entry: Anti-SARS-CoV-2 B cell receptors can mediate viral entry in an ACE2-independent mechanism.PLoS pathogens · 2026Article
- The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.Current HIV research · 2026Review
- A SARS-CoV-2 entry inhibitor trimerizes to lock the spike protein in a closed conformation.bioRxiv : the preprint server for biology · 2025Article
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Engineering B cells to Express Fully Customizable Antibodies with Enhanced Fc Functions.Research square · 2025Article
- Article
- Progress and Recent Developments in HIV Vaccine Research.Vaccines · 2025Review
- Halting Recombinant Adeno-Associated Virus Transgene Expression Using mRNA-Lipid Nanoparticle-Delivered Meganucleases.Human gene therapy · 2025Article
144 more citing papers are in PubMed but not listed here.
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34 authors.
Funding
Abstract
Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs). However, even the best bNAbs neutralize 10-50% of HIV-1 isolates inefficiently (80% inhibitory concentration (IC80) > 5 μg ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean half-maximum inhibitory concentration (IC50) < 0.05 μg ml(-1)). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2 and simian immunodeficiency virus isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46 and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17-77 μg ml(-1) of fully functional rhesus eCD4-Ig for more than 40 weeks, and these macaques were protected from several infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well-characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine.
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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.