Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report.
Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2×10(6) CFU) and low doses (2×10(2) CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNγ, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.
Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2 Bajaj Nagar, Nagpur 440 010, India.
Aliabbas A
AA
Husain
Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2 Bajaj Nagar, Nagpur 440 010, India.
Hatim F
HF
Daginawala
Department of Veterinary Microbiology and Animal Biotechnology, Nagpur Veterinary College, Nagpur 440 006, India.
Shubangi R
SR
Warke
Department of Veterinary Microbiology and Animal Biotechnology, Nagpur Veterinary College, Nagpur 440 006, India.
Devanand R
DR
Kalorey
Department of Veterinary Microbiology and Animal Biotechnology, Nagpur Veterinary College, Nagpur 440 006, India.
Nitin V
NV
Kurkure
Environmental Genomic Unit, National Environmental Engineering Research Institute (NEERI), CSIR, Nehru Marg, Nagpur-440 020, India.
Hemant J
HJ
Purohit
Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2 Bajaj Nagar, Nagpur 440 010, India.
Girdhar M
GM
Taori
Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2 Bajaj Nagar, Nagpur 440 010, India.
Rajpal S
RS
Kashyap
Immune markers; Mice; Subcutaneous route; Tuberculosis