Increased B and T cell responses in M. bovis bacille Calmette-Guérin vaccinated pigs co-immunized with plasmid DNA encoding a prototype tuberculosis antigen

Nicolas Bruffaerts, Lasse E. Pedersen, Gaëlle Vandermeulen, Véronique Préat, Norbert Stockhofe, Kris Huygen, Marta Romano

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The only tuberculosis vaccine currently available, bacille Calmette-Guérin (BCG) is a poor inducer of CD8+ T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8+ T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation. Control pigs received unformulated BCG. The BCG-pAg85A combination stimulated robust and sustained Ag85A specific antibody, lymphoproliferative, IL-6, IL-10 and IFN-γ responses. IgG1/IgG2 antibody isotype ratio reflected the Th1 helper type biased response. T lymphocyte responses against purified protein derivative of tuberculin (PPD) were induced in all (BCG) vaccinated animals, but responses were much stronger in BCG-pAg85A vaccinated pigs. Finally, Ag85A-specific IFN-γ producing CD8+ T cells were detected by intracellular cytokine staining and a synthetic peptide, spanning Ag85A131-150 and encompassing two regions with strong predicted SLA-1∗0401/SLA-1∗0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG-plasmid DNA co-administration.

Original languageEnglish
Article numbere0132288
JournalPLoS ONE
Volume10
Issue number7
DOIs
Publication statusPublished - 14 Jul 2015

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T-cells
tuberculosis
prototypes
B-lymphocytes
plasmids
Tuberculosis
Plasmids
B-Lymphocytes
Swine
T-lymphocytes
Tuberculosis Vaccines
antigens
T-Lymphocytes
Antigens
Animals
swine
DNA
Immunoglobulin G
vaccines
Latent Tuberculosis

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Bruffaerts, Nicolas ; Pedersen, Lasse E. ; Vandermeulen, Gaëlle ; Préat, Véronique ; Stockhofe, Norbert ; Huygen, Kris ; Romano, Marta. / Increased B and T cell responses in M. bovis bacille Calmette-Guérin vaccinated pigs co-immunized with plasmid DNA encoding a prototype tuberculosis antigen. In: PLoS ONE. 2015 ; Vol. 10, No. 7.
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title = "Increased B and T cell responses in M. bovis bacille Calmette-Gu{\'e}rin vaccinated pigs co-immunized with plasmid DNA encoding a prototype tuberculosis antigen",
abstract = "The only tuberculosis vaccine currently available, bacille Calmette-Gu{\'e}rin (BCG) is a poor inducer of CD8+ T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8+ T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation. Control pigs received unformulated BCG. The BCG-pAg85A combination stimulated robust and sustained Ag85A specific antibody, lymphoproliferative, IL-6, IL-10 and IFN-γ responses. IgG1/IgG2 antibody isotype ratio reflected the Th1 helper type biased response. T lymphocyte responses against purified protein derivative of tuberculin (PPD) were induced in all (BCG) vaccinated animals, but responses were much stronger in BCG-pAg85A vaccinated pigs. Finally, Ag85A-specific IFN-γ producing CD8+ T cells were detected by intracellular cytokine staining and a synthetic peptide, spanning Ag85A131-150 and encompassing two regions with strong predicted SLA-1∗0401/SLA-1∗0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG-plasmid DNA co-administration.",
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Increased B and T cell responses in M. bovis bacille Calmette-Guérin vaccinated pigs co-immunized with plasmid DNA encoding a prototype tuberculosis antigen. / Bruffaerts, Nicolas; Pedersen, Lasse E.; Vandermeulen, Gaëlle; Préat, Véronique; Stockhofe, Norbert; Huygen, Kris; Romano, Marta.

In: PLoS ONE, Vol. 10, No. 7, e0132288, 14.07.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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AU - Pedersen, Lasse E.

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