title: Application of mycobacterial proteomics to vaccine design: improved protection by Mycobacterium bovis BCG prime-Rv3407 DNA boost vaccination against tuberculosis.
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.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.forename: Leander
authors.initials: L
authors.lastname: Grode
authors.forename: Jens
authors.initials: J
authors.lastname: Mattow
authors.forename: Maik
authors.initials: M
authors.lastname: Stein
authors.forename: Peggy
authors.initials: P
authors.lastname: Mann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Knapp
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ulmer
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D020543:Proteome; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D020543:Proteome; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma