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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
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 perfringoly...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582491/ https://www.ncbi.nlm.nih.gov/pubmed/19023426 http://dx.doi.org/10.1371/journal.pone.0003790 |
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author | Magalhaes, Isabelle Sizemore, Donata R. Ahmed, Raija K. Mueller, Stefanie Wehlin, Lena Scanga, Charles Weichold, Frank Schirru, Giulia Pau, Maria Grazia Goudsmit, Jaap Kühlmann-Berenzon, Sharon Spångberg, Mats Andersson, Jan Gaines, Hans Thorstensson, Rigmor Skeiky, Yasir A. W. Sadoff, Jerry Maeurer, Markus |
author_facet | Magalhaes, Isabelle Sizemore, Donata R. Ahmed, Raija K. Mueller, Stefanie Wehlin, Lena Scanga, Charles Weichold, Frank Schirru, Giulia Pau, Maria Grazia Goudsmit, Jaap Kühlmann-Berenzon, Sharon Spångberg, Mats Andersson, Jan Gaines, Hans Thorstensson, Rigmor Skeiky, Yasir A. W. Sadoff, Jerry Maeurer, Markus |
author_sort | Magalhaes, Isabelle |
collection | PubMed |
description | 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 (<200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha(+) T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha(+) T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity. CONCLUSION: AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials |
format | Text |
id | pubmed-2582491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25824912008-11-21 rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector Magalhaes, Isabelle Sizemore, Donata R. Ahmed, Raija K. Mueller, Stefanie Wehlin, Lena Scanga, Charles Weichold, Frank Schirru, Giulia Pau, Maria Grazia Goudsmit, Jaap Kühlmann-Berenzon, Sharon Spångberg, Mats Andersson, Jan Gaines, Hans Thorstensson, Rigmor Skeiky, Yasir A. W. Sadoff, Jerry Maeurer, Markus PLoS One Research Article 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 (<200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha(+) T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha(+) T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity. CONCLUSION: AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials Public Library of Science 2008-11-21 /pmc/articles/PMC2582491/ /pubmed/19023426 http://dx.doi.org/10.1371/journal.pone.0003790 Text en Magalhaes et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Magalhaes, Isabelle Sizemore, Donata R. Ahmed, Raija K. Mueller, Stefanie Wehlin, Lena Scanga, Charles Weichold, Frank Schirru, Giulia Pau, Maria Grazia Goudsmit, Jaap Kühlmann-Berenzon, Sharon Spångberg, Mats Andersson, Jan Gaines, Hans Thorstensson, Rigmor Skeiky, Yasir A. W. Sadoff, Jerry Maeurer, Markus rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title | rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title_full | rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title_fullStr | rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title_full_unstemmed | rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title_short | rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector |
title_sort | rbcg induces strong antigen-specific t cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582491/ https://www.ncbi.nlm.nih.gov/pubmed/19023426 http://dx.doi.org/10.1371/journal.pone.0003790 |
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