TY - JOUR T1 - Lymph node targeting of BCG vaccines amplifies CD4 and CD8 T-cell responses and protection against Mycobacterium tuberculosis34032 JF - Vaccine Y1 - 2013 A1 - Waeckerle-Men,Y. A1 - Nicolas Bruffaerts A1 - Liang,Y. A1 - Fabienne Jurion A1 - Sander,P. A1 - Kundig,T.M. A1 - K Huygen A1 - Johansen,P. KW - 0 KW - a KW - administration & dosage KW - Animals KW - article KW - BCG KW - BCG Vaccine KW - Benefit KW - benefits KW - CD4-Positive T-Lymphocytes KW - CD8-Positive T-Lymphocytes KW - Cell KW - Cell Proliferation KW - cells KW - Comparative Study KW - Cytokines KW - Development KW - Disease Models,Animal KW - dissemination KW - effective KW - electronic KW - Female KW - Frequency KW - Help KW - hospital KW - im KW - immune response KW - Immunisation KW - immunology KW - injection KW - Injections,Intradermal KW - Injections,Intralymphatic KW - Injections,Subcutaneous KW - intradermal KW - IS KW - journal KW - Lymph Nodes KW - lymphocyte KW - Lymphocytes KW - M KW - methods KW - mice KW - Mice,Inbred C57BL KW - Mycobacterium KW - Mycobacterium bovis KW - Mycobacterium tuberculosis KW - Objective KW - pathogenicity KW - prevention & control KW - problems KW - production KW - protection KW - Pulmonary KW - recombinant KW - Research KW - Research Support KW - response KW - Responses KW - risk KW - SB - IM KW - secretion KW - Strategies KW - Strategy KW - study KW - Switzerland KW - Test KW - time KW - Times KW - Tuberculosis KW - Tuberculosis,Pulmonary KW - Universities KW - university KW - university hospital KW - Vaccination KW - vaccine KW - vaccines KW - varieties KW - variety AB - 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-alpha, IL-2, IL-17 and, especially, IFN-gamma secretion by. CD4 and CD8 T cells. Most importantly, intralymphatic vaccination with 2x10(3)CFU BCG induced sustained protection against M. tuberculosis in intratracheally challenged C57BL/6 mice, whereas subcutaneous vaccination with 2x10(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 VL - 31 CP - 7 U1 - 34032 M3 - http://dx.doi.org/10.1016/j.vaccine.2012.12.034 ER -