Prime-boost with Mycobacterium smegmatis recombinant vaccine improves protection in mice infected with Mycobacterium tuberculosis

Ana Paula Junqueira-Kipnis, Fábio Muniz De Oliveira, Monalisa Martins Trentini, Sangeeta Tiwari, Bing Chen, Danilo Pires Resende, Bruna D.S. Silva, Mei Chen, Lydia Tesfa, William R. Jacobs, André Kipnis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The development of a new vaccine as a substitute for Bacillus Calmette-Guerin or to improve its efficacy is one of the many World Health Organization goals to control tuberculosis. Mycobacterial vectors have been used successfully in the development of vaccines against tuberculosis. To enhance the potential utility of Mycobacterium smegmatis as a vaccine, it was transformed with a recombinant plasmid containing the partial sequences of the genes Ag85c, MPT51 , and HspX (CMX) from M. tuberculosis. The newly generated recombinant strain mc2-CMX was tested in a murine model of infection. The recombinant vaccine induced specific IgG1 or IgG2a responses to CMX. CD4+ and CD8+ T cells from the lungs and spleen responded ex vivo to CMX, producing IFN-γ, IL17, TNF-α, and IL2. The vaccine thus induced a significant immune response in mice. Mice vaccinated with mc 2-CMX and challenged with M. tuberculosis showed better protection than mice immunized with wild-type M. smegmatis or BCG. To increase the safety and immunogenicity of the CMX antigens, we used a recombinant strain of M. smegmatis, IKE (immune killing evasion), to express CMX. The recombinant vaccine IKE-CMX induced a better protective response than mc2-CMX. The data presented here suggest that the expression of CMX antigens improves the immune response and the protection induced in mice when M. smegmatis is used as vaccine against tuberculosis.

Original languageEnglish (US)
Article numbere78639
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 8 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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