title: Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen.
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.
authors.affiliation: Service Immunology, Scientific Institute for Public Health (WIV-ISP Site Ukkel), Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bruffaerts
authors.affiliation: Section for Immunology and Vaccinology, Technical University of Denmark, Bulowsvej Frederiksberg C, Denmark.
authors.forename: Lasse E
authors.initials: LE
authors.lastname: Pedersen
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Division Infection Biology Central Veterinary Institute, Part of Wageningen U(niversity)&R(esearch); Lelystad, The Netherlands.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stockhofe-Zurwieden
authors.affiliation: Service Immunology, Scientific Institute for Public Health (WIV-ISP Site Ukkel), Brussels, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.affiliation: Service Immunology, Scientific Institute for Public Health (WIV-ISP Site Ukkel), Brussels, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Romano
mesh_terms: D000483:Alleles; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D013045:Species Specificity; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D007371:Interferon-gamma