A PE_PGRS33 protein of Mycobacterium tuberculosis: an ideal target for future tuberculosis vaccine design

Abstract

It is known that cellular immune response is relevant to fight against tuberculosis (TB); hence, identification of mycobacterial antigens that induce a protective immune cellular response is of great interest, especially for the development of effective TB vaccines. Genomic data have an impact on the identification of potential antigens as new vaccine targets. In this review, we summarize the current knowledge about the advances in new TB vaccine designs as well as the features reported for the pro-glu_polymorphic GC-rich sequence (PE_PGRS33) protein, considering this molecule as a prototype of the PE_PGRS family to better understand the biological function of this protein family that could be considered an ideal target for future vaccine design.

Keywords:

• BCG
• PE_PGRS
• PE_PGRS33
• subunit vaccine
• tuberculosis

Acknowledgements

The authors are thankful for the writing assistance utilized in the production of this manuscript: editorial support was provided by an in-house editing service from Informa Healthcare.

Financial & competing interests disclosure

This manuscript was supported by SEP-CONACYT 83224-2007. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Tuberculosis (TB) is the second leading cause of death worldwide from an infectious disease perspective.

• Bacillus Calmette-Guérin is the only approved vaccine against TB.

• Neonatal vaccination with Bacillus Calmette-Guérin provides protection against meningeal TB but does not appear to be effective in preventing pulmonary TB in adults.

• New approaches in TB vaccines focus on subunit vaccines as well as DNA or virus vector-based vaccines that express mycobacterial antigens.

• Several studies have suggested that PE_PGRS proteins of M. tuberculosis are a source of T- and B-cell antigens, and some of them are being evaluated for possible inclusion in new TB vaccines.

• The PE_PGRS33 protein encoded by the Rv1818c gene is the most studied member of PE_PGRS family.

• The major antibody response is directed toward epitopes located in the PGRS domain of the PE_PGRS33 protein and epitopes of the PE domain are responsible for induction of cellular immune response.

• Variations in the polymorphic repeats of the PGRS domain modulate the innate immune response.

• The PE_PGRS33 protein could be a potential candidate for a new subunit vaccine.