Surface expression of MPT64 as a fusion with the PE domain of PE_PGRS33 enhances Mycobacterium bovis BCG protective activity against Mycobacterium tuberculosis in mice

Michela Sali, Gabriele Di Sante, Francesco Ria, Giovanni Fadda, Giovanni Delogu, Antonella Zumbo, Annabella Procoli, Matteo Morandi, Alessandro Cascioferro, Valentina Donà, Stefano Rocca, Giorgio Palù, Riccardo Manganelli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

33 Citazioni (Scopus)

Abstract

To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain (H)PE-ΔMPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with (H)PE-ΔMPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement (at both 28 and 70 days postchallenge), (ii) rBCG strains expressing MPT64 provide better protection than the parental BCG strain only when this antigen is surface expressed, and (iii) the (H)PE-ΔMPT64-BCG-induced MPT64-specific T cell repertoire when characterized by β chain variable region-β chain joining region (BV-BJ) spectratyping indicates that protection is correlated with the ability to recruit gamma interferon (IFN-γ)-secreting T cells carrying the BV8.3-BJ1.5 (172 bp) shared rearrangement. These results demonstrate that (H)PE-ΔMPT64-BCG is one of the most effective new vaccines tested so far in the mouse model of tuberculosis and underscore the impact of antigen cellular localization on the induction of the specific immune response induced by rBCG.
Lingua originaleEnglish
pagine (da-a)5202-5213
Numero di pagine12
RivistaInfection and Immunity
Volume78
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Animals
  • Antigens, Bacterial
  • Antigens, Surface
  • Artificial Gene Fusion
  • BCG Vaccine
  • Bacterial Proteins
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Interferon-gamma
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell
  • Tuberculosis
  • Vaccines, Synthetic

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