PD-1 Blockade in Rhesus Macaques: Impact on Chronic Infection and Prophylactic Vaccination
| العنوان: | PD-1 Blockade in Rhesus Macaques: Impact on Chronic Infection and Prophylactic Vaccination |
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| المؤلفون: | Danilo R. Casimiro, John W. Shiver, Meizhen Feng, Kara S. Cox, David B. Olsen, James P. Guare, Fengsheng Li, Daniel C. Freed, Daria J. Hazuda, Michael D. Miller, Tong-Ming Fu, Adam C. Finnefrock, Aimin Tang, Kara J. Sykes |
| المصدر: | The Journal of Immunology. 182:980-987 |
| بيانات النشر: | The American Association of Immunologists, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | T cell, Programmed Cell Death 1 Receptor, Immunology, Simian Acquired Immunodeficiency Syndrome, B7-H1 Antigen, Epitope, Cell Line, Viral vector, Mice, Immune system, Antigens, CD, medicine, Animals, Humans, Immunology and Allergy, Antibodies, Blocking, Mice, Inbred BALB C, biology, SAIDS Vaccines, Antibodies, Monoclonal, Viral Load, biology.organism_classification, Macaca mulatta, Blockade, Chronic infection, Rhesus macaque, medicine.anatomical_structure, Immunoglobulin G, Chronic Disease, Apoptosis Regulatory Proteins, Viral load |
| الوصف: | Programmed Cell Death 1 (PD-1) plays a crucial role in immunomodulation. Binding of PD-1 to its ligand receptors down-regulates immune responses, and published reports suggest that this immune modulation is exploited in cases of tumor progression or chronic viral infection to evade immune surveillance. Thus, blockade of this signal could restore or enhance host immune functions. To test this hypothesis, we generated a panel of mAbs specific to human PD-1 that block PD ligand 1 and tested them for in vitro binding, blocking, and functional T cell responses, and evaluated a lead candidate in two in vivo rhesus macaque (Macaca mulatta) models. In the first therapeutic model, chronically SIV-infected macaques were treated with a single infusion of anti-PD-1 mAb; viral loads increased transiently before returning to, or falling below, pretreatment baselines. In the second prophylactic model, naive macaques were immunized with an SIV-gag adenovirus vector vaccine. Induced PD-1 blockade caused a statistically significant (p < 0.05) increase in the peak percentage of T cells specific for the CM9 Gag epitope. These new results on PD-1 blockade in nonhuman primates point to a broader role for PD-1 immunomodulation and to potential applications in humans. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da1ac3e921039f5f19d0471dede95aa3Test https://doi.org/10.4049/jimmunol.182.2.980Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....da1ac3e921039f5f19d0471dede95aa3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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