Comparative analysis of different vaccine constructs expressing defined antigens from Mycobacterium tuberculosis.

BACKGROUND Studies of different vaccine constructs have demonstrated variable efficacy against Mycobacterium tuberculosis in animal models. Despite the fact that these vaccines have used one or another of a very small number of immunodominant antigens, a direct comparison of the relative efficacy of the antigens and delivery systems has been difficult, because the studies have used different parameters for assessment. METHODS We compared the efficacies of the most commonly used vaccine constructs--adjuvanted protein, plasmid DNA, and live bacterial vectors--bearing the immunodominant secreted antigens early secreted antigen target-6 and antigen 85B, either alone or as a fusion protein. Mice were vaccinated with these constructs, and the effects of different delivery systems on protective efficacy (as assessed by survival studies and by monitoring bacterial load) and antigen-specific responses (including the contribution of CD4 and CD8 T cells to these responses) were assayed by various methods. RESULTS The relative efficacy of different vaccines is dependent on the delivery system, the antigen, and the animal model. Likewise, the relative immunodominance of individual antigens in the fusion molecule is altered by the choice of delivery system. CONCLUSION These results clearly demonstrate the importance of assessing vaccine function by use of multiple parameters and indicate which parameters are most reliable for assessing vaccine efficacy.

[1]  P. Andersen,et al.  Combination of the Cationic Surfactant Dimethyl Dioctadecyl Ammonium Bromide and Synthetic Mycobacterial Cord Factor as an Efficient Adjuvant for Tuberculosis Subunit Vaccines , 2004, Infection and Immunity.

[2]  K. Huygen.  On the Use of DNA Vaccines for the Prophylaxis of Mycobacterial Diseases , 2003, Infection and Immunity.

[3]  P. Andersen,et al.  Selecting the components for a safe and efficient tuberculosis subunit vaccine--recent progress and post-genomic insights. , 2003, Current pharmaceutical biotechnology.

[4]  P. Andersen,et al.  Tuberculosis vaccine development. , 2002, Current opinion in pulmonary medicine.

[5]  R. Appelberg,et al.  Failure of the Mycobacterium bovis BCG Vaccine: Some Species of Environmental Mycobacteria Block Multiplication of BCG and Induction of Protective Immunity to Tuberculosis , 2002, Infection and Immunity.

[6]  R. Appelberg,et al.  Failure to induce enhanced protection against tuberculosis by increasing T‐cell‐dependent interferon‐γ generation , 2001, Immunology.

[7]  S. Kaufmann,et al.  How can immunology contribute to the control of tuberculosis? , 2001, Nature Reviews Immunology.

[8]  M. Chan-yeung,et al.  Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong. , 2001, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[9]  H. Mollenkopf,et al.  Protective efficacy against tuberculosis of ESAT-6 secreted by a live Salmonella typhimurium vaccine carrier strain and expressed by naked DNA. , 2001, Vaccine.

[10]  P. Andersen,et al.  Protection of Mice with a Tuberculosis Subunit Vaccine Based on a Fusion Protein of Antigen 85B and ESAT-6 , 2001, Infection and Immunity.

[11]  M. Thakur,et al.  Global tuberculosis control report. , 2001, The National medical journal of India.

[12]  E. Agger,et al.  Tuberculosis subunit vaccine development: on the role of interferon-gamma. , 2001, Vaccine.

[13]  I. Orme,et al.  Tuberculosis vaccine development: recent progress. , 2001, Trends in microbiology.

[14]  P. Andersen,et al.  TB vaccines: progress and problems. , 2001, Trends in immunology.

[15]  H. McShane,et al.  Enhanced Immunogenicity of CD4+ T-Cell Responses and Protective Efficacy of a DNA-Modified Vaccinia Virus Ankara Prime-Boost Vaccination Regimen for Murine Tuberculosis , 2001, Infection and Immunity.

[16]  M. Horwitz,et al.  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. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  H. Dockrell,et al.  Vaccinia expression of Mycobacterium tuberculosis-secreted proteins: tissue plasminogen activator signal sequence enhances expression and immunogenicity of M. tuberculosis Ag85. , 2000, Microbes and infection.

[18]  Stefan H. E. Kaufmann,et al.  Is the development of a new tuberculosis vaccine possible? , 2000, Nature Medicine.

[19]  D. Young,et al.  The 19‐kD antigen and protective immunity in a murine model of tuberculosis , 2000, Clinical and experimental immunology.

[20]  W. Goebel,et al.  Protection against murine tuberculosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the 30-kDa antigen of Mycobacterium bovis BCG. , 2000, FEMS immunology and medical microbiology.

[21]  P. Andersen,et al.  ESAT-6 Subunit Vaccination againstMycobacterium tuberculosis , 2000, Infection and Immunity.

[22]  A. Apt,et al.  Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice. , 2000, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[23]  C. Dye,et al.  A cost-benefit analysis of BCG revaccination in the Czech Republic. , 1999, Vaccine.

[24]  W. Britton,et al.  Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis. , 1999, Infection and immunity.

[25]  J. Ulmer,et al.  Vaccination with Plasmid DNA Encoding Mycobacterial Antigen 85A Stimulates a CD4+ and CD8+T-Cell Epitopic Repertoire Broader than That Stimulated byMycobacterium tuberculosis H37Rv Infection , 1998, Infection and Immunity.

[26]  P. Andersen,et al.  B-Cell Epitopes and Quantification of the ESAT-6 Protein of Mycobacterium tuberculosis , 1998, Infection and Immunity.

[27]  J. Ulmer,et al.  Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex. , 1997, Vaccine.

[28]  J. Lamb,et al.  Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae , 1997, Infection and immunity.

[29]  Global Tuberculosis Programme.  Global tuberculosis control : WHO report , 1997 .

[30]  S. Mittal,et al.  Does B.C.G. vaccination prevent or postpone the occurrence of tuberculous meningitis? , 1996, Indian journal of pediatrics.

[31]  Donna L. Montgomery,et al.  Immunogenicity and protective efficacy of a tuberculosis DNA vaccine , 1996, Nature Medicine.

[32]  W. Goebel,et al.  Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. E. M. Fine,et al.  Variation in protection by BCG: implications of and for heterologous immunity , 1995, The Lancet.

[34]  C S Berkey,et al.  The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. , 1995, Pediatrics.

[35]  J. Vuust,et al.  Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli , 1995, Clinical and diagnostic laboratory immunology.

[36]  I. Sjögren.  Tuberculosis in BCG vaccinated and unvaccinated young Swedish men. A comparative study. , 1976, Bulletin of the International Union against Tuberculosis.