Skip to main content

Advertisement

SpringerLink
Log in

Immunogenicity of recombinant BCG vaccine strains overexpressing components of the antigen 85 complex of Mycobacterium tuberculosis

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

The components of antigen 85 complex of Mycobacterium tuberculosis (Ag 85A, Ag 85B and Ag 85C), due to their immunodominant and secretory nature, represent promising protective antigen candidates and have been used in numerous vaccine preparations. We have used recombinant Bacille Calmette Guerin (BCG) strains overexpressing Ag 85A and Ag 85C to immunize BALB/c mice to investigate the immunogenicity of these strains. Mice immunized with recombinant BCG strains exhibited an increased humoral immune response when compared to mice immunized with wild-type BCG. The recombinant BCG strain overexpressing Ag 85A also induced an increased Th1-like response, characterized by elevated levels of IFN-γ in antigen stimulated splenocyte cultures and a strong IgG2a antibody response, when compared to wild-type BCG. Immunization with recombinant BCG strain overexpressing Ag 85C, on the other hand did not elicit increased IFN-γ secretion on restimulation of splenocytes in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  1. Andersen P (2001) TB vaccines: progress and problems. Trends Immunol 22:160–168

    Article  CAS  PubMed  Google Scholar 

  2. Baldwin SL, D'Souza C, Roberts AD, Kelly BP, Frank AA, Lui MA, Ulmer JB, Huygen K, McMurray DM, Orme IM (1998) Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis. Infect Immun 66:2951–2959

    CAS  PubMed  Google Scholar 

  3. Baldwin SL, D'Souza CD, Orme IM, Liu MA, Huygen K, Denis O, Tang A, Zhu L, Montgomery D, Ulmer JB (1999) Immunogenicity and protective efficacy of DNA vaccines encoding secreted and non-secreted forms of Mycobacterium tuberculosis Ag85A. Tuberc Lung Dis 79:251–259

    Article  CAS  Google Scholar 

  4. Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ, Besra GS (1997) Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276:1420–1422

    Article  CAS  PubMed  Google Scholar 

  5. Bloom BR, Fine PEM (1994) The BCG experience: implications for future vaccines against tuberculosis. In Bloom BR (ed) Tuberculosis: pathogenesis, protection and control. American Society of Microbiology, Washington, DC, pp 531–557

    Google Scholar 

  6. Dhar N, Rao V, Tyagi AK (2000) Recombinant BCG approach for development of vaccines: cloning and expression of immunodominant antigens of M. tuberculosis. FEMS Microbiol Lett 190:309–316

    Article  CAS  PubMed  Google Scholar 

  7. Dolin PJ, Raviglione MC, Kochi A (1994) Global tuberculosis incidence and mortality during 1990–2000. Bull World Health Org 72:213–220

    CAS  PubMed  Google Scholar 

  8. Flynn JL, Chan J, Triebold JE, Dalton DK, Stewart TA, Bloom BR (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    CAS  PubMed  Google Scholar 

  9. Horwitz MA, Lee BW, Dillon BJ, Harth G (1995) Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 92:1530–1534

    CAS  PubMed  Google Scholar 

  10. Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic S (2000) Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. Proc Natl Acad Sci USA 97:13853–13858

    CAS  PubMed  Google Scholar 

  11. Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, Deck RR, DeWitt CM, Orme IM, Baldwin S, D'Souza C, Drowart A, Lozes E, Vanderbussche P, Van Vooren JP, Liu MA, Ulmer JB (1996) Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med 2:893–898

    CAS  PubMed  Google Scholar 

  12. Kamath AT, Feng CG, Macdonald M, Briscoe H, Britton WJ (1999) Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis. Infect Immun 67:1702–1707

    CAS  PubMed  Google Scholar 

  13. Kamath AT, Groat NL, Bean AG, Britton WJ (2000) Protective effect of DNA immunization against mycobacterial infection is associated with the early emergence of interferon-gamma (IFN-gamma)-secreting lymphocytes. Clin Exp Immunol 120:476–482

    Article  CAS  PubMed  Google Scholar 

  14. Lozes E, Huygen K, Content J, Denis O, Montgomery D, Yawman AM, Vandenbussche P, Van Vooren JP, Drowart A, Ulmer JB, Liu MA (1997) Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex. Vaccine 15:830–833

    Article  CAS  PubMed  Google Scholar 

  15. Malin AS, Huygen K, Content J, Mackett M, Brandt L, Andersen P, Smith SM, Dockrell HM (2000) Vaccinia expression of Mycobacterium tuberculosis-secreted proteins: tissue plasminogen activator signal sequence enhances expression and immunogenicity of M. tuberculosis Ag85. Microbes Infect 2:1677–1685

    Article  CAS  PubMed  Google Scholar 

  16. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173

    CAS  PubMed  Google Scholar 

  17. Ohara N, Yamada T (2001) Recombinant BCG vaccines. Vaccine 19:4089–4098

    Article  CAS  PubMed  Google Scholar 

  18. Ohara N, Matsuoka M, Nomaguchi H, Naito M, Yamada T (2000) Inhibition of multiplication of Mycobacterium leprae in mouse foot pads by recombinant Bacillus Catmette-Guerin (BCG). Vaccine 18:1294–1297

    Article  CAS  PubMed  Google Scholar 

  19. Ohara N, Matsuoka M, Nomaguchi H, Naito M, Yamada T (2001) Protective responses against experimental Mycobacterium leprae infection in mice induced by recombinant Bacillus Calmette-Guerin over-producing three putative protective antigen candidates. Vaccine 19:1906–1910

    Article  CAS  PubMed  Google Scholar 

  20. Tanghe A, Denis O, Lambrecht B, Motte V, Berg T van den, Huygen K (2000) Tuberculosis DNA vaccine encoding Ag85A is immunogenic and protective when administered by intramuscular needle injection but not by epidermal gene gun bombardment. Infect Immun 68:3854–3860

    Article  CAS  PubMed  Google Scholar 

  21. Wiker HG, Harboe M (1992) The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis. Microbiol Rev 56:648–661

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Department of Biotechnology, Government of India. N.D. and V.R. are thankful to the University Grants Commission, India for Senior Research Fellowships. The technical assistance of Bindu Nair is acknowledged. Rajiv Chawla is acknowledged for efficient secretarial assistance.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021 India

    Neeraj Dhar, Vivek Rao & Anil K. Tyagi

Authors
  1. Neeraj Dhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vivek Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anil K. Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anil K. Tyagi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dhar, N., Rao, V. & Tyagi, A.K. Immunogenicity of recombinant BCG vaccine strains overexpressing components of the antigen 85 complex of Mycobacterium tuberculosis . Med Microbiol Immunol 193, 19–25 (2004). https://doi.org/10.1007/s00430-002-0170-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-002-0170-x

Keywords

Search

Navigation