ArticleMolecular therapy. Methods & clinical development2022
AAV-monoclonal antibody expression protects mice from Ebola virus without impeding the endogenous antibody response to heterologous challenge.
Article in Molecular therapy. Methods & clinical development, 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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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.Vaccines · 2026Review
- Research hotspots and trend analyses of maximum biosafety level pathogens: A bibliometric study using China's 2023 catalogue of pathogens as an example.Biosafety and health · 2026Article
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- Adeno-associated virus delivery of anti-alpha toxin monoclonal antibodies confers protection against Staphylococcus aureus infections.PLoS pathogens · 2026Article
- Nucleic acid-encoded antibody gene transfer-next generation of antibody therapies.Drug delivery · 2025Review
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections.Pharmaceutics · 2024Review
- AAV-vectored expression of monospecific or bispecific monoclonal antibodies protects mice from lethal Pseudomonas aeruginosa pneumonia.Gene therapy · 2024Article
- AAV-Vectored Expression of Marburg Virus-Neutralizing Antibody MR191 Provides Complete Protection From Challenge in a Guinea Pig Model.The Journal of infectious diseases · 2023Article
- Development of AAV-delivered broadly neutralizing anti-human ACE2 antibodies against SARS-CoV-2 variants.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy.Antibodies (Basel, Switzerland) · 2023Review
- rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19.Frontiers in immunology · 2023Article
- Overcoming Barriers to Preventing and TreatingBiomedicines · 2022Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Filoviruses cause severe hemorrhagic fever with case fatality rates as high as 90%. Filovirus-specific monoclonal antibodies (mAbs) confer protection in nonhuman primates as late as 5 days after challenge, and FDA-approved mAbs REGN-EB3 and mAb114 have demonstrated efficacy against Ebola virus (EBOV) infection in humans. Vectorized antibody expression mediated by adeno-associated virus (AAV) can generate protective and sustained concentrations of therapeutic mAbs in animal models for a variety of infectious diseases, including EBOV. Here we demonstrate that AAV6.2FF-mediated expression of murine IgG2a EBOV mAbs, 2G4 and 5D2, protects from mouse-adapted (MA)-EBOV infection with none of the surviving mice developing anti-VP40 antibodies above background. Protective serum concentrations of AAV6.2FF-2G4/AAV6.2FF-5D2 did not alter endogenous antibody responses to heterologous virus infection. AAV-mediated expression of EBOV mAbs 100 and 114, and pan-ebolavirus mAbs, FVM04, ADI-15878, and CA45, as human IgG1 antibodies conferred protection against MA-EBOV at low serum concentrations, with minimum protective serum levels as low as 2 μg/mL. Vectorized expression of murine IgG2a or human IgG1 mAbs led to sustained expression in the serum of mice for >400 days or for the lifetime of the animal, respectively. AAV6.2FF-mediated mAb expression offers an alternative to recombinant antibody administration in scenarios where long-term protection is preferable to passive immunization.
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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.