Martin W J, Marcus S
J Bacteriol. 1966 May;91(5):1750-8. doi: 10.1128/jb.91.5.1750-1758.1966.
Martin, William J. (University of Utah, Salt Lake City), and Stanley Marcus. Detoxified bacterial endotoxins. II. Preparation and biological properties of chemically modified crude endotoxins from Salmonella typhimurium. J. Bacteriol. 91:1750-1758. 1966.-Chemical modification of a crude endotoxin prepared by the Roschka-Edwards (RE) procedure from a strain of Salmonella typhimurium yielded products which were nontoxic for mice and had reduced fever effects in rabbits. A reduction in rabbit pyrogenicity of approximately 100 times was noted with a potassium periodate-treated RE preparation when compared with the parent RE preparation. Measured in a similar fashion, pyrogenicity of a potassium methylate-treated RE preparation was reduced by a factor of 10 while pyrogenicity of a boron trifluoride RE preparation was unchanged. All of these endotoxoids, including the parent RE preparation, showed little toxicity for mice. Immunogenicity was determined in mice by comparing Boivin, RE, and endotoxoid preparations with a heat-killed, phenol-preserved (HP) vaccine prepared from the same strain of S. typhimurium. Employing a 10 ld(50) challenge, the protective immunogenicity of the respective vaccines was determined by active immunized mouse protection tests. Although two 100 mug immunizing doses of the Boivin, RE, and the respective endotoxoid preparations varied in mouse protection (potassium methylate RE > Boivin > RE > boron trifluoride RE > potassium periodate RE), it was evident that, with the exception of the potassium methylate preparation, the HP vaccine yielded greatest protection against the 10 ld(50) challenge with S. typhimurium. Further mouse protection experiments suggested that the minimal immunogenic dose of the potassium methylate RE vaccine preparation was approximately 50 mug. These data indicated an approximate fivefold difference between the minimal pyrogenic dose (10 mug) and the minimal immunogenic dose (50 mug). These findings further suggest that potassium methylate RE vaccine preparations should be considered in the search for less toxic enteric fever vaccines.
马丁，威廉·J.（犹他大学，盐湖城）和斯坦利·马库斯。解毒细菌内毒素。II. 鼠伤寒沙门氏菌化学修饰粗制内毒素的制备及生物学特性。《细菌学杂志》91:1750 - 1758。1966年。——用罗施卡 - 爱德华兹（RE）方法从一株鼠伤寒沙门氏菌制备的粗制内毒素经化学修饰后，得到的产物对小鼠无毒，对兔子的发热作用减弱。与未处理的RE制剂相比，高碘酸钾处理的RE制剂使兔子的致热原性降低了约100倍。以类似方式测量，甲醇钾处理的RE制剂的致热原性降低了10倍，而三氟化硼处理的RE制剂的致热原性未变。所有这些类毒素，包括未处理的RE制剂，对小鼠几乎没有毒性。通过将博伊文、RE和类毒素制剂与用同一株鼠伤寒沙门氏菌制备的热灭活、苯酚保存（HP）疫苗在小鼠中比较来确定免疫原性。采用10个半数致死量（ld(50)）的攻击剂量，通过主动免疫小鼠保护试验来确定各自疫苗的保护性免疫原性。尽管两次100微克的免疫剂量下，博伊文、RE和各自的类毒素制剂在小鼠保护方面存在差异（甲醇钾处理的RE > 博伊文 > RE > 三氟化硼处理的RE > 高碘酸钾处理的RE），但很明显，除了甲醇钾处理的制剂外，HP疫苗对10个ld(50)剂量的鼠伤寒沙门氏菌攻击提供了最大的保护。进一步的小鼠保护实验表明，甲醇钾处理的RE疫苗制剂的最小免疫原剂量约为50微克。这些数据表明最小致热剂量（10微克）和最小免疫原剂量（50微克）之间大约相差五倍。这些发现进一步表明，在寻找毒性较小的伤寒疫苗时应考虑甲醇钾处理的RE疫苗制剂。
