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Increased B and T Cell Responses in M. bovis Bacille Calmette-Guerin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen
Pedersen, L.E. Vandermeulen, G. Preat, V. Stockhofe-Zurwieden, N. Huygen, K
Pedersen, L.E.
Vandermeulen, G.
Preat, V.
Stockhofe-Zurwieden, N.
Huygen, K
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Abstract
The only tuberculosis vaccine currently available, bacille Calmette-Guerin (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-gamma 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-gamma 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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2015-07-14
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Peer reviewed scientific article
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journal.pone_.0132288.pdf
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ALL, alternative, Animal, Animals, antibodies, Antibody, article, AS, BCG, Belgium, Biology, Brussels, Cell, cells, Combination, concept, Control, de, delivery, denmark, Dna, DNA vaccines, DRUG, electronic, health, im, immunology, INFECTION, Institute, intradermal, IS, journal, lymphocyte, M, MODEL, Netherlands, Pig, Pigs, protection, protein, public, public health, Public-health, Ratio, region, Research, response, Responses, SB - IM, Service, Species, specific, study, Synthetic, The Netherlands, Tuberculosis, Type, Universities, university, vaccine, vaccines, Vector, veterinary, WIV-ISP