Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens

Priscille Brodin, Laleh Majlessi, Roland Brosch, Debbie Smith, Gregory Bancroft, Simon Clark, Ann Williams, Claude Leclerc, Stewart T. Cole*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

Mycobacterium microti, the vole bacillus, which was used as a live vaccine against tuberculosis until the 1970s, confers the same protection in humans as does Mycobacterium bovis bacille Calmette-Guérin (BCG). However, because the efficacy of the BCG vaccine varies considerably, we have tried to develop a better vaccine by reintroducing into M. microti the complete region of difference 1 (RD1), which is required for secretion of the potent T cell antigens early secreted antigen target (ESAT)-6 and culture filtrate protein (CFP)-10. The resultant recombinant strain, M. microti OV254::RD1-2F9, induced specific ESAT-6 and CFP-10 immune responses in mice with CD8+ T lymphocytes that had strong expression of the CD44hi activation marker. This vaccine also displayed better efficacy against disseminated disease in the mouse and the guinea pig models of tuberculosis than was seen in animals vaccinated with M. microti alone or with BCG. The M. microti OV254: :RD1-2F9 vaccine was less virulent and persistent in mice and than was BCG::RD1-2F9 may represent a safer alternative to BCG::RD1-2F9.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalJournal of Infectious Diseases
Volume190
Issue number1
DOIs
Publication statusPublished - 1 Jul 2004

Bibliographical note

Funding Information:
Received 15 October 2003; accepted 29 December 2003; electronically published 4 June 2004. Presented in part: Keystone Symposia, Tuberculosis: Integrating Host and Pathogen Biology, Taos, NM, 25–30 January 2003 (poster 212). Financial support: European Community (grant CT-1999-01093); Association Franc¸aise Raoul Follereau; Institut Pasteur (grant PTR 110/2002). Reprints or correspondence: Dr. Stewart Cole, Unité de Génétique Moléculaire Bactérienne, 28 rue du Docteur Roux, 75724 Paris, Cedex 15, France (stcole@ pasteur.fr).

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