Limits...
Immunogenicity and protective efficacy against murine tuberculosis of a prime-boost regimen with BCG and a DNA vaccine expressing ESAT-6 and Ag85A fusion protein.

Lu J, Wang C, Zhou Z, Zhang Y, Cao T, Shi C, Chen Z, Chen L, Cai C, Fan X - Clin. Dev. Immunol. (2011)

Bottom Line: The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population.The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone.Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

ABSTRACT
Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB) vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A) expressing the fusion protein of Ag85A and ESAT-6 (r685A) and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulent Mycobacterium tuberculosis H37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

Show MeSH

Related in: MedlinePlus

r685A-specific IgG antibody-induced in immunized mice. Mice were immunized and bled at day 14 following the last immunization; serum antibody levels were assessed by ELISA. Sera from five animals in each group were evaluated individually at the dilutions indicated. Results shown are the mean and standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3065234&req=5

fig5: r685A-specific IgG antibody-induced in immunized mice. Mice were immunized and bled at day 14 following the last immunization; serum antibody levels were assessed by ELISA. Sera from five animals in each group were evaluated individually at the dilutions indicated. Results shown are the mean and standard error.

Mentions: Sera IgG antibodies against r685A protein were determined by ELISA. As shown in Figure 5, strong IgG response to r685A protein was elicited in BCG, pcD685A, BCG plus vector, and BCG plus pcD685A-treated mice groups. As expected, empty DNA vector and control groups stimulated little or very weak IgG response.


Immunogenicity and protective efficacy against murine tuberculosis of a prime-boost regimen with BCG and a DNA vaccine expressing ESAT-6 and Ag85A fusion protein.

Lu J, Wang C, Zhou Z, Zhang Y, Cao T, Shi C, Chen Z, Chen L, Cai C, Fan X - Clin. Dev. Immunol. (2011)

r685A-specific IgG antibody-induced in immunized mice. Mice were immunized and bled at day 14 following the last immunization; serum antibody levels were assessed by ELISA. Sera from five animals in each group were evaluated individually at the dilutions indicated. Results shown are the mean and standard error.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065234&req=5

fig5: r685A-specific IgG antibody-induced in immunized mice. Mice were immunized and bled at day 14 following the last immunization; serum antibody levels were assessed by ELISA. Sera from five animals in each group were evaluated individually at the dilutions indicated. Results shown are the mean and standard error.
Mentions: Sera IgG antibodies against r685A protein were determined by ELISA. As shown in Figure 5, strong IgG response to r685A protein was elicited in BCG, pcD685A, BCG plus vector, and BCG plus pcD685A-treated mice groups. As expected, empty DNA vector and control groups stimulated little or very weak IgG response.

Bottom Line: The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population.The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone.Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.

ABSTRACT
Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB) vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A) expressing the fusion protein of Ag85A and ESAT-6 (r685A) and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulent Mycobacterium tuberculosis H37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

Show MeSH
Related in: MedlinePlus