| Abstract | Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone. |
| Authors | Hans Joachim Mollenkopf, Leander Grode, Jens Mattow, Maik Stein, Peggy Mann, Bernhard Knapp, Jeffrey Ulmer, Stefan H E Kaufmann
(Affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.)
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| Journal | Infection and immunity
(Infect Immun)
Vol. 72
Issue 11
Pg. 6471-9
(Nov 2004)
ISSN: 0019-9567 United States |
| PMID | 15501778
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antibodies, Bacterial
- Antigens, Bacterial
- BCG Vaccine
- Bacterial Proteins
- Proteome
- Tuberculosis Vaccines
- Vaccines, DNA
- Interferon-gamma
|
| Topics |
- Animals
- Antibodies, Bacterial
(blood)
- Antigens, Bacterial
(genetics, immunology, metabolism)
- BCG Vaccine
(immunology)
- Bacterial Proteins
(genetics, immunology, metabolism)
- Cattle
- Computational Biology
- Drug Design
- Humans
- Immunization, Secondary
- Interferon-gamma
(metabolism)
- Mice
- Mice, Inbred BALB C
- Mycobacterium bovis
(immunology, metabolism)
- Mycobacterium tuberculosis
(immunology, metabolism)
- Proteome
- Tuberculosis
(prevention & control)
- Tuberculosis Vaccines
(immunology)
- Vaccination
- Vaccines, DNA
(immunology)
|
