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

作者：Lindsey Devin R; Dhandayuthapani Subramanian; Jagannath Chinnaswamy^*

来源：Tuberculosis, 2009, 89: S46-S48.

DOI：10.1016/s1472-9792(09)70011-3

• Vaccine
• Mycobacterium smegmatis
• Tuberculosis

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 (MsmOEAg85B) and compared the immunogenicity of MsmOEAg85B with that of wild-type Msm. Mice which were vaccinated with either Msm or MsmOEAg85B 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, MsmOEAg85B induced enhanced CD4+IFN gamma+ 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 MsmOEAg85B-vaccinated mice. Lungs of Msm-OEAg85B-vaccinated mice showed increased numbers of CD4+IFN gamma+ 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 MsmOEAg85B 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.

• 出版日期2009-12