Background The PPE protein family of Mycobacterium tuberculosis includes 69 proteins rich in glycine and together with the PE protein family accounts for ~10% of the coding capacity of the M. tuberculosis genome. Little is known about their function but their polymorphic nature suggests that they represent antigens of immunological relevance. In this investigation, we have evaluated the vaccine potential of a M. tuberculosis antigen of the PPE protein family, namely PPE44 (Rv2770c). Methods PPE44-specific immune responses generated by an infection with M. tuberculosis of mice were analyzed and the immunogenicity and protective efficacy of a plasmid DNA vaccine coding for PPE44 (pDNA-PPE44) and of recombinant PPE44 protein formulated in DDA adjuvant (rec-PPE44) were evaluated. Results PPE44-specific immune responses could be detected in mice acutely, chronically and latently infected with M. tuberculosis. Vaccination of C57BL/6 and BALB/c mice with pDNA-PPE44 and rec-PPE44 generated strong cellular and humoral antigen-specific immune responses and immunodominant IL-2+/IFN-γ+ and IFN-γ+/cytotoxic T cell epitopes were identified using overlapping synthetic peptides covering the entire PPE44 sequence. Most importantly, vaccination of C57BL/6 mice with pDNA-PPE44 and rec-PPE44 followed by an intratracheal challenge with virulent M. tuberculosis resulted in a protective efficacy comparable to the one afforded by BCG in terms of reduction in bacterial load in the lungs. Conclusions PPE44 of M. tuberculosis is a protective antigen that could be included in novel subunit TB vaccines. Its protective efficacy contributes to focus attention on the PPE protein family as a source of TB vaccine candidates.
Protective activity of tuberculosis subunit vaccines expressing PPE44 (Rv2770c)
RINDI, LAURA;GARZELLI, CARLO;
2008-01-01
Abstract
Background The PPE protein family of Mycobacterium tuberculosis includes 69 proteins rich in glycine and together with the PE protein family accounts for ~10% of the coding capacity of the M. tuberculosis genome. Little is known about their function but their polymorphic nature suggests that they represent antigens of immunological relevance. In this investigation, we have evaluated the vaccine potential of a M. tuberculosis antigen of the PPE protein family, namely PPE44 (Rv2770c). Methods PPE44-specific immune responses generated by an infection with M. tuberculosis of mice were analyzed and the immunogenicity and protective efficacy of a plasmid DNA vaccine coding for PPE44 (pDNA-PPE44) and of recombinant PPE44 protein formulated in DDA adjuvant (rec-PPE44) were evaluated. Results PPE44-specific immune responses could be detected in mice acutely, chronically and latently infected with M. tuberculosis. Vaccination of C57BL/6 and BALB/c mice with pDNA-PPE44 and rec-PPE44 generated strong cellular and humoral antigen-specific immune responses and immunodominant IL-2+/IFN-γ+ and IFN-γ+/cytotoxic T cell epitopes were identified using overlapping synthetic peptides covering the entire PPE44 sequence. Most importantly, vaccination of C57BL/6 mice with pDNA-PPE44 and rec-PPE44 followed by an intratracheal challenge with virulent M. tuberculosis resulted in a protective efficacy comparable to the one afforded by BCG in terms of reduction in bacterial load in the lungs. Conclusions PPE44 of M. tuberculosis is a protective antigen that could be included in novel subunit TB vaccines. Its protective efficacy contributes to focus attention on the PPE protein family as a source of TB vaccine candidates.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
