Neonatal BCG immunization followed by DNAhsp65 boosters: highly immunogenic but not protective against tuberculosis - a paradoxical effect of the vector?
| Autor: | Ana Paula Masson, Juliana Seger, Célio Lopes Silva, Sofia Fernanda Gonçalves Zorzella-Pezavento, A. C. Pelizon, Rozalino Santos, Alexandrina Sartori, Denise Morais da Fonseca, L. A. Justulin, Douglas Rodrigues Martins |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP) |
| Rok vydání: | 2010 |
| Předmět: |
Tuberculosis
Immunology Immunization Secondary complex mixtures Mycobacterium tuberculosis Mice Immune system Bacterial Proteins medicine Vaccines DNA Animals Mycobacterium leprae Antigens Bacterial Mice Inbred BALB C biology business.industry Immunogenicity General Medicine Chaperonin 60 medicine.disease biology.organism_classification Antibodies Bacterial Vaccination Animals Newborn BCG Vaccine Cytokines business Tuberculosis vaccines BCG vaccine |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1365-3083 |
| Popis: | Made available in DSpace on 2013-09-27T14:54:31Z (GMT). No. of bitstreams: 1 WOS000273688300001.pdf: 288439 bytes, checksum: 6044356f046cdd0c18b0c237b16a5877 (MD5) Previous issue date: 2010-02-01 Made available in DSpace on 2013-09-30T18:38:39Z (GMT). No. of bitstreams: 1 WOS000273688300001.pdf: 288439 bytes, checksum: 6044356f046cdd0c18b0c237b16a5877 (MD5) Previous issue date: 2010-02-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:51:14Z No. of bitstreams: 1 WOS000273688300001.pdf: 288439 bytes, checksum: 6044356f046cdd0c18b0c237b16a5877 (MD5) Made available in DSpace on 2014-05-20T13:51:14Z (GMT). No. of bitstreams: 1 WOS000273688300001.pdf: 288439 bytes, checksum: 6044356f046cdd0c18b0c237b16a5877 (MD5) Previous issue date: 2010-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis. São Paulo State Univ UNESP, Dept Microbiol Immunol, Biosci Inst, BR-18618000 São Paulo, Brazil São Paulo State Univ UNESP, Dept Morphol, Biosci Inst, BR-18618000 São Paulo, Brazil Univ São Paulo, Dept Biochem & Immunol, São Paulo, Brazil São Paulo State Univ UNESP, Dept Microbiol Immunol, Biosci Inst, BR-18618000 São Paulo, Brazil São Paulo State Univ UNESP, Dept Morphol, Biosci Inst, BR-18618000 São Paulo, Brazil FAPESP: 03/06348-7 |
| Databáze: | OpenAIRE |
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