Behr M A, Small P M
Department of Medicine, Stanford University School of Medicine, CA, USA.
Vaccine. 1999 Feb 26;17(7-8):915-22. doi: 10.1016/s0264-410x(98)00277-1.
Bacillus Calmette-Guérin (BCG) is the name given to a family of vaccines derived in 1921 by the in-vitro attenuation of Mycobacterium bovis. Subsequently, BCG seed lots were distributed globally, and both phenotypic and genotypic differences between strains have been described. As a step to understanding BCG diversity, we have reviewed the English and French historical record on 13 strains and DNA was extracted from these strains for restriction-fragment-length-polymorphism study. The written record suggests "early strains" obtained from the Pasteur Institute between 1924 and 1926 and "later strains" obtained after 1931. Molecular typing resulted in 3 clades, based on variability in IS6110-typing and the presence of mpt64 gene. With two exceptions, these clades correspond with strains obtained in 1924-26 (IS6110-2/mpt64+), 1926-31 (IS6110-1/mpt64+), and 1931 or later (IS6110-1/mpt64-) This analysis demonstrates that BCG has undergone genetic changes since 1921, consistent with ongoing in-vitro evolution.
卡介苗（BCG）是1921年通过牛分枝杆菌的体外减毒而获得的一系列疫苗的名称。随后，卡介苗种子批被分发到全球，并且已经描述了不同菌株之间的表型和基因型差异。作为了解卡介苗多样性的一个步骤，我们查阅了13种菌株的英文和法文历史记录，并从这些菌株中提取了DNA用于限制性片段长度多态性研究。书面记录显示有1924年至1926年间从巴斯德研究所获得的“早期菌株”以及1931年之后获得的“后期菌株”。基于IS6110分型的变异性和mpt64基因的存在，分子分型产生了3个进化枝。除了两个例外，这些进化枝分别对应于1924 - 26年获得的菌株（IS6110 - 2/mpt64 +）、1926 - 31年获得的菌株（IS6110 - 1/mpt64 +）以及1931年或之后获得的菌株（IS6110 - 1/mpt64 -）。该分析表明，自1921年以来卡介苗经历了基因变化，这与持续的体外进化一致。
