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Effect of cationic liposomes on BCG trafficking and vaccine-induced immune responses following a subcutaneous immunization in mice
Institution:1. Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Silver Spring, MD 20993, United States;2. Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, United States;1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China;2. Wuhan Chopper Biology Co., LTD, Wuhan 430070, China;1. Department of Pathology and Laboratory Medicine, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States;2. Division of Infectious Diseases, Department of Medicine, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States;1. Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, Südufer 10, 17493 Greifswald – Insel Riems, Germany;2. Department of Epidemiology, Crisis-organization and Diagnostics, Central Veterinary Institute part of Wageningen UR, PO Box 65, 8200 AB Lelystad, Netherlands;1. Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brazil;2. Department of Internal Medicine, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brazil;3. Rheumatology Service, Hospital Universitário Lauro Wanderley, João Pessoa, PB, Brazil;1. Pediatrics Center of Excellence, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;2. Research Center for Immunodeficiencies, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;3. Molecular Immunology Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran;6. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran;1. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;2. MedImmune LLC, Mountain View, CA, USA
Abstract:While formulating Mycobacterium bovis BCG in lipid-based adjuvants has been shown to increase the vaccine's protective immunity, the biological mechanisms responsible for the enhanced potency of lipid encapsulated BCG are unknown. To assess whether mixing BCG in adjuvant increases its immunogenicity by altering post-vaccination organ distribution and persistence, mice were immunized subcutaneously with conventional BCG Pasteur or BCG formulated in DDA/TDB adjuvant and the bio-distribution of BCG bacilli was evaluated in mouse lungs, spleens, lymph nodes, and livers for up to 1 year. Although BCG was rarely detected in mouse livers, mycobacteria were found in mouse lungs, spleens, and lymph nodes for at least 1 year post-vaccination. However, at various time points during the 1 year study, the frequency of lung and spleen infections and the number of mycobacteria in infected organs of individual mice were highly variable. In contrast, mycobacteria were nearly always detected in the lymph nodes of vaccinated mice. While the frequency and extent of lymph node infections generally were not significantly different between mice vaccinated with adjuvanted or nonadjuvanted BCG preparations, multiparameter flow cytometry analysis of lymph node cells showed significantly higher frequencies of CD4+ and CD8+ T cells expressing IFN-γ and IFN-γ/TNF-α in mice immunized with adjuvanted BCG. Overall, our data suggest that the relationship between lymph node infection and the generation of anti-tuberculosis protective responses following BCG vaccination should be further investigated.
Keywords:BCG  Tuberculosis  Immunity  Adjuvants
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