Lymph node targeting of BCG vaccines amplifies CD4 and CD8 T-cell responses and protection against Mycobacterium tuberculosis

Autor: Thomas M. Kündig, Yuan Liang, Nicolas Bruffaerts, Ying Waeckerle-Men, Kris Huygen, Pål Johansen, Peter Sander, F Jurion
Přispěvatelé: University of Zurich, Johansen, Pål
Jazyk: angličtina
Rok vydání: 2013
Předmět:
CD4-Positive T-Lymphocytes
3400 General Veterinary
CD8-Positive T-Lymphocytes
Mice
0302 clinical medicine
2400 General Immunology and Microbiology
Cytotoxic T cell
Lymph node
0303 health sciences
Mycobacterium bovis
biology
10179 Institute of Medical Microbiology
Vaccination
10177 Dermatology Clinic
3. Good health
Infectious Diseases
medicine.anatomical_structure
BCG Vaccine
Molecular Medicine
Cytokines
Female
Lymph
Tuberculosis
Injections
Intradermal
Injections
Subcutaneous
610 Medicine & health
complex mixtures
Mycobacterium tuberculosis
03 medical and health sciences
Immune system
medicine
Animals
Tuberculosis
Pulmonary
030304 developmental biology
Cell Proliferation
General Veterinary
General Immunology and Microbiology
business.industry
Public Health
Environmental and Occupational Health
Injections
Intralymphatic
2739 Public Health
Environmental and Occupational Health
2725 Infectious Diseases
medicine.disease
biology.organism_classification
Virology
Mice
Inbred C57BL
Disease Models
Animal
1313 Molecular Medicine
Immunology
570 Life sciences
Lymph Nodes
business
030215 immunology
Zdroj: Vaccine
Vaccine; Vol 31
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2012.12.034
Popis: Vaccination with Mycobacterium bovis BCG provides limited protection against pulmonary tuberculosis and a risk of dissemination in immune-compromised vaccinees. For the development of new TB vaccines that stimulate strong T-cell responses a variety of strategies is being followed, especially recombinant BCG and attenuated M. tuberculosis. The objective of the current study was to test potential benefits of vaccination through direct lymph-node targeting of wildtype BCG; the recommended route of vaccination with BCG is intradermal. C57BL/6 mice were immunised with BCG by intradermal, subcutaneous or intralymphatic injections. Cellular immune responses and protection against M. tuberculosis were determined. Intralymphatic vaccination was 100-1000 times more effective in stimulating BCG-specific immune responses than intradermal or subcutaneous immunisation. Intralymphatic administration stimulated high frequencies of mycobacterium-specific lymphocytes with strong proliferating capacity and production of TNF-α, IL-2, IL-17 and, especially, IFN-γ secretion by. CD4 and CD8 T cells. Most importantly, intralymphatic vaccination with 2×10(3)CFU BCG induced sustained protection against M. tuberculosis in intratracheally challenged C57BL/6 mice, whereas subcutaneous vaccination with 2×10(5)CFU BCG conferred only a transient protection. Hence, direct administration of M. bovis BCG to lymph nodes demonstrates that efficient targeting to lymph nodes may help to overcome the efficacy problems of vaccination with BCG.
Databáze: OpenAIRE
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