Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research.
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http://dx.doi.org/10.1093/infdis/jit451 | DOI Listing |
Int J Mol Sci
January 2025
Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies, 8 Baltiyskaya Street, Moscow 125315, Russia.
Adeno-associated viruses (AAVs) are non-pathogenic, replication-deficient viruses that have gained widespread attention for their application as gene therapy vectors. While these vectors offer high transduction efficiency and long-term gene expression, the host immune response poses a significant challenge to their clinical success. This review focuses on the obstacles to evaluating the humoral response to AAVs.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
Background: The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved.
View Article and Find Full Text PDFPLoS One
January 2025
Center for Innovation in Brain Science, University of Arizona Health Sciences, Tucson, Arizona, United States of America.
Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland;
Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)--(thiophen-2-ylmethyl)pyrimidin-4-amine ([C]MC1) to detect COX-2 density in a healthy human brain. The specificity of [C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Pharmacology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, China. Electronic address:
Agonistic monoclonal antibodies targeting 4-1BB have shown much preclinical promise, but their clinical development has been limited by obvious toxicity or unremarkable efficacy. Here, we generated two humanized anti-B7H3 × 4-1BB bsAbs (HK056-001/002) by fusing an anti-4-1BB scFv to the C-terminus of an anti-B7H3 with an intact Fc fragment from human IgG1 or IgG4. The two bsAbs were able to stimulate the 4-1BB signaling pathway, which was strictly dependent on B7H3 expression.
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