초록 ▼

○ 결핵균 감염 마우스 모델에서 예방백신의 평가지표의 확립하고자 하였으며, 결해균 감염 후 2주, 4주, 8주 후에 폐와 비장 등 장기에서 결핵균 수의 측정방법, 결핵균 감염 후 마우스의 생존률 조사, 육안병변의 비교방법과 조직병변의 객관적인 비교평가, 그리고 cytokine의 측정, cytokine mRNA의 측정방법, 예방백신 접종 후 면역세포 분석 등 면역지표 측정방법을 확립하였음.
○ EU-FP7 결핵백신개발 사업단에서 개발되는 새로운 결핵백신 후보의 예방효과를 평가하고자 Pre-exposure 모델과 postexpos

○ 결핵균 감염 마우스 모델에서 예방백신의 평가지표의 확립하고자 하였으며, 결해균 감염 후 2주, 4주, 8주 후에 폐와 비장 등 장기에서 결핵균 수의 측정방법, 결핵균 감염 후 마우스의 생존률 조사, 육안병변의 비교방법과 조직병변의 객관적인 비교평가, 그리고 cytokine의 측정, cytokine mRNA의 측정방법, 예방백신 접종 후 면역세포 분석 등 면역지표 측정방법을 확립하였음.
○ EU-FP7 결핵백신개발 사업단에서 개발되는 새로운 결핵백신 후보의 예방효과를 평가하고자 Pre-exposure 모델과 postexposure모델을 확립하였으며, 희망자 공고를 통하여 요청받은 결핵균 약독백신 2종 (Rv1503c mutant; SigE-/FadDdeficientmutant)을 Beijing K 균주 감염모델을 이용하여 평가한 결과 생균백신인 결핵균 SigE-/FadD-deficient mutant는 BCG백신보다 높은 방어효과를 나타냈음.

Abstract ▼

Tuberculosis (TB) is one of the three major infectious diseases in the world inflicting more than 8 million new patients and about 1.3 million deaths each year. One of the major control strategies for TB is to develop an effective vaccine against Mycobacterium tuberculosis infection. Although BCG va

Tuberculosis (TB) is one of the three major infectious diseases in the world inflicting more than 8 million new patients and about 1.3 million deaths each year. One of the major control strategies for TB is to develop an effective vaccine against Mycobacterium tuberculosis infection. Although BCG vaccine has been used, it is known to protect severe form of TB among young children. Therefore, new TB vaccines against pulmonary TB among young adults as well as adults have been desirable. As an effort to develop such vaccines, European Union supported a series of new TB vaccine deveopment research program through the funding mechanism of Framework Program, which included TB Vaccine Initiative (TBVI) Consortium Gran in which about 30 laboratories participated for last four years.
One of the work packages in the EU-FP7 on TBVI was to evaluate new EB vaccine candidates using various animal models. In a typical animal model, M. tuberculosis H37Rv or Erdman strains have been used, whose strains are non-Beijing types. In East Asian countries including Korea, however, the majority of M. tuberculosis isolates belong to the Beijing type. Therefore, this study was initiated to evaluate new TB vaccine candidates by EU-FP7 consortium against M. tuberculosis Beijing type strain in a mouse model. M. tuberculosis H37Rv, Erdman, and Beijing K strains were used for challenging vaccinated mice with various TB vaccine candidates ncluding BCG vaccine as a control. Various parameters measuring vaccine efficacy were established and included vial cell counts in the lungs and spleesn, extensiveness of pathology lesions, survival rate, immunological parameters. Based on calling process, two live attenutated M. tuberculosis vaccine candiates (Rv1503c mutant; SigE-/ FadD-deficient mutant) were submitted for evaluation against Beijing K strain challenge mouse model. Both vaccine candidates were effective in protection, and particlarly, the M. tuberculosis SigE-/FadD-deficient mutant was more protective than BCG vaccine against Beijing K strain infection, indicating a potential new vaccine suitable in the East Asia region. In addition, a couple of new protein based vaccine candidates which are specific to the Beijing types were identified by the comparative whole genome sequences and the Ins56b protein (MTBK_24690) was effective against M. tuberculosis Beijing K strain infection. In order to overcome a weak point of C57BL/6 mouse lacking hypoxic tubercle lesion, C3HeB/FeJ mouse model was explored to establish for evaluation of TB vaccine candidates.
In summary, both pre-exposue and post-exposure mouse models of TB were established for efficacy evaluation of vaccine candidates in this study. Both live attenuated M. tuberculosis vaccines and protein-based vaccines were effective in protection against Beijing K strain, which is most prevalent in Korea, suggesting a possibility of new vaccines replacing or boosting the current BCG vaccine against TB.