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.

Skin-Based Vaccination: A Systematic Mapping Review of the Types of Vaccines and Methods Used and Immunity and Protection Elicited in Pigs

“…While there is no specific platform that stands out for the intradermal route, 83% of epidermal vaccinations use DNA platforms. Some of the studies evaluated the combination of the skin-based route of administration with intramuscular, oral, subcutaneous, or intranasal, simultaneously [ 112 , 132 ] or through heterologous prime-boost regimens using the same or different vaccines [ 111 , 122 , 142 , 147 , 150 , 202 , 206 , 208 , 217 , 223 , 229 , 234 , 238 , 261 ], with the objective to elicit a stronger immune response.…”

Live Attenuated African Swine Fever Viruses as Ideal Tools to Dissect the Mechanisms Involved in Cross-Protection

“…Despite not being statistically significant, evident differences were observed between groups when comparing the average ASFV-specific IgG1/IgG2 ratios, independently of the sera dilution used ( Figure 3 C). Thus, pigs boosted with virulent BA71 showed a clear IgG2 bias, most probably indicating the induction of more efficient Th1-like responses [ 29 ] compared with BA71∆CD2-boosted animals, which showed an equilibrated IgG1/IgG2 ratio (almost 1 in average).…”

Increasing the Vaccine Potential of Live M. bovis BCG by Coadministration with Plasmid DNA Encoding a Tuberculosis Prototype Antigen

“…bovis BCG than of Mtb is needed to induce similar CD8 + T-cell responses [ 8 ]. On the other hand, highly increased immune responses can also be detected in mice and pigs immunized with a combination of BCG and pDNA encoding the mycolyl-transferase Ag85A, which is among the most strongly expressed proteins in the culture filtrate of the BCG vaccine [ 42 ].…”