title: Immunogenicity and protective efficacy of tuberculosis DNA vaccines combining mycolyl-transferase Ag85A and phosphate transport receptor PstS-3.
abstract: DNA vaccines encoding the 32,000 MW mycolyl-transferase Ag85A and the 40,000 MW phosphate-binding protein PstS-3 can elicit protective immune responses against experimental infection with Mycobacterium tuberculosis in C57BL/6 mice. Here we have analysed the vaccine potential of a combination of both antigens using plasmid vectors expressing either a fusion protein of both antigens or the separate proteins driven by two independent promoters (in pBudCE4.1 vector). Comparable levels of Ag85A specific T helper 1 (Th1) type immune responses could be induced by the two combination vaccines and the single vaccine encoding the mycolyl-transferase, whereas induction of PstS-3 specific Th1-mediated responses was impaired in both combination vaccines. In contrast, magnitude of CD8+ mediated responses against the PstS-3 protein was comparable following combination or single DNA vaccination. Antigenic competition was also observed at the antibody level; PstS-3 specific levels being lower in mice vaccinated with the fusion vector and Ag85A specific levels being lower in mice vaccinated with the combination pBudCE4.1 vector (as compared to levels obtained following single plasmid immunization). Protection against M. tuberculosis was only modestly improved in mice vaccinated with the DNA combinations. It is possible that prior activation of Ag85A specific CD4+ T cells directed against this common mycobacterial antigen leads to cross-competition for major histocompatibility complex class II-restricted peptide complexes of the Pst-3 antigen. This may have implications for future combination vaccines using Ag85.
authors.affiliation: Mycobacterial Immunology, Pasteur Institute, Wetenschappelijk Instituut voor Volksgezondheid, Brussels, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Romano
authors.forename: Virginie
authors.initials: V
authors.lastname: Roupie
authors.forename: Xiao M
authors.initials: XM
authors.lastname: Wang
authors.forename: Olivier
authors.initials: O
authors.lastname: Denis
authors.forename: Fabienne
authors.initials: F
authors.lastname: Jurion
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Adnet
authors.forename: Rachid
authors.initials: R
authors.lastname: Laali
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000217:Acyltransferases / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006224:Cricetinae; D005260:Female; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014162:Transfection; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C102010:PstS-3 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis