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

Overview

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+IFNgamma+ 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 log(10)) and therefore protection in Msm-OEAg85B-vaccinated mice. Lungs of Msm-OEAg85B-vaccinated mice showed increased numbers of CD4+IFNgamma+ 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.