This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Delogu, G.
Right arrow Articles by Morris, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delogu, G.
Right arrow Articles by Morris, S. L.

 Previous Article  |  Next Article 

Infection and Immunity, January 2002, p. 292-302, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.292-302.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

DNA Vaccine Combinations Expressing Either Tissue Plasminogen Activator Signal Sequence Fusion Proteins or Ubiquitin-Conjugated Antigens Induce Sustained Protective Immunity in a Mouse Model of Pulmonary Tuberculosis

Giovanni Delogu,,{dagger} Amy Li, Charlene Repique, Frank Collins, and Sheldon L. Morris*

Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 15 June 2001/ Returned for modification 26 July 2001/ Accepted 18 September 2001

DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis. In this study, we evaluated the effectiveness of immunizing with combinations of 10 different tuberculosis DNA vaccines that expressed mycobacterial proteins fused at the N terminus to eukaryotic intracellular targeting sequences. In one vaccine combination, the genes were fused to the tissue plasminogen activator signal sequence (TPA), while in a second combination the same 10 genes were expressed as ubiquitin (Ub)-conjugated proteins. In ex vivo studies in which the secretion of gamma interferon was measured, cellular immune responses were detected in mice vaccinated with either the TPA DNA vaccine combination or the Ub DNA vaccine combination at 7 and 14 days following a low-dose Mycobacterium tuberculosis challenge. Moreover, mice vaccinated with the TPA combination, the Ub combination, and Mycobacterium bovis BCG were able to limit the growth of tubercle bacilli in the lung and spleen after a virulent tuberculous aerosol challenge. Histopathological analyses also showed that mice immunized with the DNA vaccine combinations had substantially improved postinfection lung pathology relative to the naïve controls. Finally, in three different long-term experiments, the survival periods following aerogenic challenge were extended as much as sevenfold for vaccinated mice compared to naïve controls. Interestingly, in all three experiments, no significant differences were detected in the mean times to death for mice immunized with the TPA combination or the Ub combination relative to the BCG controls. In conclusion, these studies demonstrate the effectiveness of immunization with DNA vaccine combinations against tuberculosis and suggest that further testing of these plasmid cocktails is warranted.


* Corresponding author. Mailing address: LMDCI/OVRR/CBER/FDA, HFM-431, Building 29, Room 502, 29 Lincoln Dr., Bethesda, MD 20892. Phone: (301) 496-5978. Fax: (301) 402-2776. E-mail: morris{at}cber.fda.gov.

Editor: J. D. Clements

{dagger} Present address: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.


Infection and Immunity, January 2002, p. 292-302, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.292-302.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Parra, M., Yang, A. L., Lim, J., Kolibab, K., Derrick, S., Cadieux, N., Perera, L. P., Jacobs, W. R., Brennan, M., Morris, S. L. (2009). Development of a Murine Mycobacterial Growth Inhibition Assay for Evaluating Vaccines against Mycobacterium tuberculosis. CVI 16: 1025-1032 [Abstract] [Full Text]  
  • Lim, J., Derrick, S. C., Kolibab, K., Yang, A. L., Porcelli, S., Jacobs, W. R., Morris, S. L. (2009). Early Pulmonary Cytokine and Chemokine Responses in Mice Immunized with Three Different Vaccines against Mycobacterium tuberculosis Determined by PCR Array. CVI 16: 122-126 [Abstract] [Full Text]  
  • Jeon, B. Y., Derrick, S. C., Lim, J., Kolibab, K., Dheenadhayalan, V., Yang, A. L., Kreiswirth, B., Morris, S. L. (2008). Mycobacterium bovis BCG Immunization Induces Protective Immunity against Nine Different Mycobacterium tuberculosis Strains in Mice. Infect. Immun. 76: 5173-5180 [Abstract] [Full Text]  
  • Wu, Y., Woodworth, J. S., Shin, D. S., Morris, S., Behar, S. M. (2008). Vaccine-Elicited 10-Kilodalton Culture Filtrate Protein-Specific CD8+ T Cells Are Sufficient To Mediate Protection against Mycobacterium tuberculosis Infection. Infect. Immun. 76: 2249-2255 [Abstract] [Full Text]  
  • Delogu, G., Sanguinetti, M., Posteraro, B., Rocca, S., Zanetti, S., Fadda, G. (2006). The hbhA Gene of Mycobacterium tuberculosis Is Specifically Upregulated in the Lungs but Not in the Spleens of Aerogenically Infected Mice.. Infect. Immun. 74: 3006-3011 [Abstract] [Full Text]  
  • Parra, M., Cadieux, N., Pickett, T., Dheenadhayalan, V., Brennan, M. J. (2006). A PE Protein Expressed by Mycobacterium avium Is an Effective T-Cell Immunogen. Infect. Immun. 74: 786-789 [Abstract] [Full Text]  
  • Talaat, A. M., Stemke-Hale, K. (2005). Expression Library Immunization: a Road Map for Discovery of Vaccines against Infectious Diseases. Infect. Immun. 73: 7089-7098 [Full Text]  
  • Derrick, S. C., Yang, A. L., Morris, S. L. (2005). Vaccination with a Sindbis Virus-Based DNA Vaccine Expressing Antigen 85B Induces Protective Immunity against Mycobacterium tuberculosis. Infect. Immun. 73: 7727-7735 [Abstract] [Full Text]  
  • Segal, S., Pollard, A. J. (2005). Vaccines against bacterial meningitis. Br Med Bull 72: 65-81 [Abstract] [Full Text]  
  • Parra, M., Pickett, T., Delogu, G., Dheenadhayalan, V., Debrie, A.-S., Locht, C., Brennan, M. J. (2004). The Mycobacterial Heparin-Binding Hemagglutinin Is a Protective Antigen in the Mouse Aerosol Challenge Model of Tuberculosis. Infect. Immun. 72: 6799-6805 [Abstract] [Full Text]  
  • Derrick, S. C., Repique, C., Snoy, P., Yang, A. L., Morris, S. (2004). Immunization with a DNA Vaccine Cocktail Protects Mice Lacking CD4 Cells against an Aerogenic Infection with Mycobacterium tuberculosis. Infect. Immun. 72: 1685-1692 [Abstract] [Full Text]  
  • Huygen, K. (2003). On the Use of DNA Vaccines for the Prophylaxis of Mycobacterial Diseases. Infect. Immun. 71: 1613-1621 [Full Text]  
  • Repique, C. J., Li, A., Collins, F. M., Morris, S. L. (2002). DNA Immunization in a Mouse Model of Latent Tuberculosis: Effect of DNA Vaccination on Reactivation of Disease and on Reinfection with a Secondary Challenge. Infect. Immun. 70: 3318-3323 [Abstract] [Full Text]  
  • Jiang, C., Magee, D. M., Ivey, F. D., Cox, R. A. (2002). Role of Signal Sequence in Vaccine-Induced Protection against Experimental Coccidioidomycosis. Infect. Immun. 70: 3539-3545 [Abstract] [Full Text]