ArticlePloS one2014
An AAV vector-mediated gene delivery approach facilitates reconstitution of functional human CD8+ T cells in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Establishing human immune system mice: application, opportunity, and challenges.Experimental & molecular medicine · 2026Review
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Article
- Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines.Vaccines · 2024Article
- Vector-Mediated Delivery of Human Major Histocompatibility Complex-I into Hepatocytes Enables Investigation of T Cell Receptor-Redirected Hepatitis B Virus-Specific T Cells in Mice, and in Macaque Cell Cultures.Human gene therapy · 2023Article
- Short Carbon Nanotube-Based Delivery of mRNA for HIV-1 Vaccines.Biomolecules · 2023Article
- Production of Humanized Mice through Stem Cell Transfer.Current protocols · 2023Article
- Viral delivery of a peptide-based immunomodulator enhances T cell priming during vaccination.Frontiers in pharmacology · 2022Article
- Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.Frontiers in immunology · 2021Article
- Understanding Normal and Malignant Human Hematopoiesis Using Next-Generation Humanized Mice.Trends in immunology · 2020Review
- Autologously Humanized Mice for Immune-Oncologic Studies.Current protocols in pharmacology · 2020Article
- Functional Human CD141+ Dendritic Cells in Human Immune System Mice.The Journal of infectious diseases · 2020Article
- Targeted Co-delivery of Tumor Antigen and α-Galactosylceramide to CD141Frontiers in immunology · 2020Article
- Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia.Journal of virology · 2019Article
- Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Humanized mouse models of immunological diseases and precision medicine.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Review
- Vaccination With Sporozoites: Models and Correlates of Protection.Frontiers in immunology · 2019Review
- AAV-Vectored Fms-Related Tyrosine Kinase 3 Ligand Inhibits CD34Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2018Article
- Gene Therapy with an Adeno-Associated Viral Vector Expressing Human Interleukin-2 Alters Immune System Homeostasis in Humanized Mice.Human gene therapy · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study, a novel adeno-associated virus (AAV) vector-mediated gene delivery approach was taken to improve the reconstitution of functional CD8(+) T cells in humanized mice, thereby mimicking the human immune system (HIS). Human genes encoding HLA-A2 and selected human cytokines (A2/hucytokines) were introduced to an immune-deficient mouse model [NOD/SCID/IL2rγ(null) (NSG) mice] using AAV serotype 9 (AAV9) vectors, followed by transplantation of human hematopoietic stem cells. NSG mice transduced with AAV9 encoding A2/hucytokines resulted in higher levels of reconstitution of human CD45(+) cells compared to NSG mice transduced with AAV9 encoding HLA-A2 alone or HLA-A2-transgenic NSG mice. Furthermore, this group of HIS mice also mounted the highest level of antigen-specific A2-restricted human CD8(+) T-cell response upon vaccination with recombinant adenoviruses expressing human malaria and HIV antigens. Finally, the human CD8(+) T-cell response induced in human malaria vaccine-immunized HIS mice was shown to be functional by displaying cytotoxic activity against hepatocytes that express the human malaria antigen in the context of A2 molecules. Taken together, our data show that AAV vector-mediated gene delivery is a simple and efficient method to transfer multiple human genes to immune-deficient mice, thus facilitating successful reconstitution of HIS in mice. The HIS mice generated in this study should ultimately allow us to swiftly evaluate the T-cell immunogenicity of various human vaccine candidates in a pre-clinical setting.
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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.