Anti-tuberculosis immunity induced in mice by vaccination with Mycobacterium smegmatis over-expressing Antigen 85B is due to the increased influx of IFNγ-positive CD4 T cells into the lungs

Devin R. Lindsey, Subramanian Dhandayuthapani, Chinnaswamy Jagannath

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

BCG vaccine is unsafe for use in patients with AIDS. Mycobacterium smegmatis (Msm), an avirulent species unlike virulent Mycobacterium tuberculosis (H37Rv, Mtb) has been used as a carrier vaccine with ambiguous results due to the elicitation of poor immune responses to antigens in mice. In this study, we over-expressed the immunodominant antigen 85B in M. smegmatis (Msm-OEAg85B) and compared the immunogenicity of Msm-OEAg85B with that of wild-type Msm. Mice which were vaccinated with either Msm or Msm-OEAg85B and challenged 2 weeks later with Mtb. Vaccine-induced protection and lung T cell responses were evaluated post vaccination and post challenge. Unlike wild-type Msm that elicited minimal T cell responses in mice, MsmOE-Ag85B induced enhanced CD4+IFNγ+ T cell responses that leveled off over 2 weeks. After virulent challenge at 2 weeks, Mtb grew progressively in the lungs of naive mice and mice vaccinated with wild-type Msm, but showed reduced growth (<0.6 log10) and therefore protection in Msm-OEAg85B-vaccinated mice. Lungs of Msm-OEAg85B-vaccinated mice showed increased numbers of CD4+IFNγ+ T cells suggesting that the reduced bacterial growth was likely due to the enhanced T cell response in lungs. Since wild-type Msm was unable to protect but Msm-OEAg85B was, we suggest that Msm can be genetically manipulated to over-express selected Mtb antigens, thereby paving the way for safer vaccines that can be used in immunodeficient patients.

Original languageEnglish (US)
Pages (from-to)S46-S48
JournalTuberculosis
Volume89
Issue numberSUPPL.1
DOIs
StatePublished - Dec 2009
Externally publishedYes

Keywords

  • Mycobacterium smegmatis
  • Tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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