Warning: Differences in the copy number of duplication unit 2 (DU2) within BCG Danish 1331 may influence findings involving genetically modified BCG Danish strains

摘要

Jain et al. [1] recently modified BCG Danish 1331, a live vaccine against tuberculosis, to over-express iron co-factored superoxide dismutase (SodA). The modification reduced BCG's ability to induce immune responses and protection in guinea pigs. Although the authors state that their findings were contrary to expectations, the results were anticipated by prior reports. In 2001 we found that SodA inhibits host responses to Mycobacterium tuberculosis[2]. In 2009 we described enhanced immune responses and protection in mice vaccinated with a recombinant BCG Tice vaccine exhibiting 3 modifications including diminished SodA activity [3]. Furthermore, I have hypothesized that increases in the activity of SodA and other antioxidants resulting from mutations in BCG during decades of in vitro cultivation explains the poor efficacy of some BCG daughter strains against pulmonary TB [4]. The authors’ findings support this hypothesis.