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

Bruffaerts N, Romano M, Denis O, Jurion F, Huygen K - Vaccines (Basel) (2014)

Bottom Line: Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA vector, as measured by Th1-type spleen cell cytokine secretion, specific IgG antibodies, as well as specific IFN-γ producing/cytolytic-CD8⁺ T-cells.Moreover, we observed a bystander activation induced by the coding plasmid, resulting in increased immune responses against other non-plasmid encoded, but BCG-expressed, antigens.In all, these results provide a proof of concept for a new TB vaccine, based on a BCG-plasmid DNA combination.

View Article: PubMed Central - PubMed

Affiliation: Scientific Institute of Public Health, Communicable and Infectious Diseases, Immunology, Brussels 1180, Belgium. nicolas.bruffaerts@wiv-isp.be.

ABSTRACT
The attenuated live M. bovis Bacille-Calmette-Guérin (BCG) is still the sole vaccine used against tuberculosis, but confers only variable efficacy against adult pulmonary tuberculosis (TB). Though no clear explanation for this limited efficacy has been given, different hypotheses have been advanced, such as the waning of memory T-cell responses, a reduced antigenic repertoire and the inability to induce effective CD8⁺ T-cell responses, which are known to be essential for latent tuberculosis control. In this study, a new BCG-based vaccination protocol was studied, in which BCG was formulated in combination with a plasmid DNA vaccine. As BCG is routinely administered to neonates, we have evaluated a more realistic approach of a simultaneous intradermal coadministration of BCG with pDNA encoding the prototype antigen, PPE44. Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA vector, as measured by Th1-type spleen cell cytokine secretion, specific IgG antibodies, as well as specific IFN-γ producing/cytolytic-CD8⁺ T-cells. Moreover, we observed a bystander activation induced by the coding plasmid, resulting in increased immune responses against other non-plasmid encoded, but BCG-expressed, antigens. In all, these results provide a proof of concept for a new TB vaccine, based on a BCG-plasmid DNA combination.

No MeSH data available.


Related in: MedlinePlus

Specific antibody production induced by BCG/pDNA co-vaccination. Anti-PPE44 (A) and anti-OVA (B) IgG-isotype antibodies were measured by ELISA in serum harvested three weeks after the last immunization. Optical density levels of serial two-fold serum dilutions are presented as the mean ± standard error of the mean and representative of two independent experiments, including five to six mice per group.
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vaccines-02-00181-f005: Specific antibody production induced by BCG/pDNA co-vaccination. Anti-PPE44 (A) and anti-OVA (B) IgG-isotype antibodies were measured by ELISA in serum harvested three weeks after the last immunization. Optical density levels of serial two-fold serum dilutions are presented as the mean ± standard error of the mean and representative of two independent experiments, including five to six mice per group.

Mentions: Total anti-PPE44 and anti-OVA IgG levels were measured in sera (Figure 5). BCG/coding-pDNA coimmunization increased the specific antibody levels to the corresponding antigen as compared to the levels observed in both BCG control groups and to levels observed after intramuscular vaccination with coding pDNA. Anti-PPE44 end-point titers in BCG/pDNA-PPE44 coimmunized mice were about thirty-fold higher than in BCG or BCG/control pDNA vaccinated mice and about nine-fold higher than in pDNA-PPE44 vaccinated mice. Anti-OVA end-point titers in coimmunized mice were about twenty-fold and nine-fold higher when compared, respectively, to BCG or BCG/control pDNA vaccinated mice and to coding pDNA vaccinated mice. Anti-PPE44 and anti-OVA end-point titers measured in BCG vaccinated mice and BCG/control pDNA co-vaccinated mice were not significantly different from the titers measured in naive mice. As for the IFN-γ responses, antibody titers in the BCG/pDNA coimmunized animals were higher than in the mice vaccinated with coding plasmid.


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

Bruffaerts N, Romano M, Denis O, Jurion F, Huygen K - Vaccines (Basel) (2014)

Specific antibody production induced by BCG/pDNA co-vaccination. Anti-PPE44 (A) and anti-OVA (B) IgG-isotype antibodies were measured by ELISA in serum harvested three weeks after the last immunization. Optical density levels of serial two-fold serum dilutions are presented as the mean ± standard error of the mean and representative of two independent experiments, including five to six mice per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494193&req=5

vaccines-02-00181-f005: Specific antibody production induced by BCG/pDNA co-vaccination. Anti-PPE44 (A) and anti-OVA (B) IgG-isotype antibodies were measured by ELISA in serum harvested three weeks after the last immunization. Optical density levels of serial two-fold serum dilutions are presented as the mean ± standard error of the mean and representative of two independent experiments, including five to six mice per group.
Mentions: Total anti-PPE44 and anti-OVA IgG levels were measured in sera (Figure 5). BCG/coding-pDNA coimmunization increased the specific antibody levels to the corresponding antigen as compared to the levels observed in both BCG control groups and to levels observed after intramuscular vaccination with coding pDNA. Anti-PPE44 end-point titers in BCG/pDNA-PPE44 coimmunized mice were about thirty-fold higher than in BCG or BCG/control pDNA vaccinated mice and about nine-fold higher than in pDNA-PPE44 vaccinated mice. Anti-OVA end-point titers in coimmunized mice were about twenty-fold and nine-fold higher when compared, respectively, to BCG or BCG/control pDNA vaccinated mice and to coding pDNA vaccinated mice. Anti-PPE44 and anti-OVA end-point titers measured in BCG vaccinated mice and BCG/control pDNA co-vaccinated mice were not significantly different from the titers measured in naive mice. As for the IFN-γ responses, antibody titers in the BCG/pDNA coimmunized animals were higher than in the mice vaccinated with coding plasmid.

Bottom Line: Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA vector, as measured by Th1-type spleen cell cytokine secretion, specific IgG antibodies, as well as specific IFN-γ producing/cytolytic-CD8⁺ T-cells.Moreover, we observed a bystander activation induced by the coding plasmid, resulting in increased immune responses against other non-plasmid encoded, but BCG-expressed, antigens.In all, these results provide a proof of concept for a new TB vaccine, based on a BCG-plasmid DNA combination.

View Article: PubMed Central - PubMed

Affiliation: Scientific Institute of Public Health, Communicable and Infectious Diseases, Immunology, Brussels 1180, Belgium. nicolas.bruffaerts@wiv-isp.be.

ABSTRACT
The attenuated live M. bovis Bacille-Calmette-Guérin (BCG) is still the sole vaccine used against tuberculosis, but confers only variable efficacy against adult pulmonary tuberculosis (TB). Though no clear explanation for this limited efficacy has been given, different hypotheses have been advanced, such as the waning of memory T-cell responses, a reduced antigenic repertoire and the inability to induce effective CD8⁺ T-cell responses, which are known to be essential for latent tuberculosis control. In this study, a new BCG-based vaccination protocol was studied, in which BCG was formulated in combination with a plasmid DNA vaccine. As BCG is routinely administered to neonates, we have evaluated a more realistic approach of a simultaneous intradermal coadministration of BCG with pDNA encoding the prototype antigen, PPE44. Strongly increased T- and B-cell responses were observed with this protocol in C57BL/6 mice when compared to the administration of only BCG or in combination with an empty pDNA vector, as measured by Th1-type spleen cell cytokine secretion, specific IgG antibodies, as well as specific IFN-γ producing/cytolytic-CD8⁺ T-cells. Moreover, we observed a bystander activation induced by the coding plasmid, resulting in increased immune responses against other non-plasmid encoded, but BCG-expressed, antigens. In all, these results provide a proof of concept for a new TB vaccine, based on a BCG-plasmid DNA combination.

No MeSH data available.


Related in: MedlinePlus