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rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector
- Source :
- PLoS ONE, 3(11). Public Library of Science, PLoS ONE, Vol 3, Iss 11, p e3790 (2008), PLoS ONE
- Publication Year :
- 2008
-
Abstract
- BACKGROUND: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta). Control animals received diluent (3 animals). METHODS AND FINDINGS: Cellular immune responses were analyzed longitudinally (12 blood draws for each animal) using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma), T cell proliferation was measured in CD4(+), CD8alpha/beta(+), and CD8alpha/alpha(+) T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA) using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i) increased Ag85B-specific IFN-gamma production in the WBA assay (median >400 pg/ml for 6 animals) one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (
- Subjects :
- T-Lymphocytes
T cell
Immunology
Bacterial Toxins
Genetic Vectors
Immunization, Secondary
lcsh:Medicine
Biology
Lymphocyte Activation
Peripheral blood mononuclear cell
Adenoviridae
Infectious Diseases/Bacterial Infections
Hemolysin Proteins
Interferon-gamma
Immune system
Immunology/Immunity to Infections
medicine
Animals
Cytotoxic T cell
Interferon gamma
Tuberculosis Vaccines
lcsh:Science
Antigens, Bacterial
Immunity, Cellular
Vaccines, Synthetic
Multidisciplinary
Infectious Diseases/Respiratory Infections
lcsh:R
Macaca mulatta
Virology
Infectious Diseases
medicine.anatomical_structure
Immunology/Immune Response
BCG Vaccine
Female
lcsh:Q
Tuberculosis vaccines
BCG vaccine
Research Article
Blood drawing
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, 3(11). Public Library of Science, PLoS ONE, Vol 3, Iss 11, p e3790 (2008), PLoS ONE
- Accession number :
- edsair.doi.dedup.....4b61509c3ec83c0790d777bbb13ae1ac