National Institute of Child Health and Human Development and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3213-6. doi: 10.1073/pnas.1324149111. Epub 2014 Feb 20.
To overcome the limitations of the current pertussis vaccines, those of limited duration of action and failure to induce direct killing of Bordetella pertussis, a synthetic scheme was devised for preparing a conjugate vaccine composed of the Bordetella bronchiseptica core oligosaccharide with one terminal trisaccharide to aminooxylated BSA via their terminal ketodeoxyoctanate residues. Conjugate-induced antibodies, by a fraction of an estimated human dose injected into young outbred mice as a saline solution, were bactericidal against B. pertussis, and their titers correlated with their ELISA values. The carrier protein is planned to be genetically altered pertussis toxoid. Such conjugates are easy to prepare, stable, and should add both to the level and duration of immunity induced by current vaccine-induced pertussis antibodies and reduce the circulation of B. pertussis.
为了克服当前百日咳疫苗的局限性，即作用持续时间有限且不能直接杀死百日咳博德特氏菌，设计了一种合成方案，用于制备一种结合疫苗，该疫苗由博德特氏菌支气管败血亚种核心寡糖与一个末端三糖通过其末端酮脱氧辛酸盐残基与氨氧基化 BSA 组成。通过将估计人类剂量的一小部分作为生理盐水注入异系幼鼠中，结合诱导的抗体对百日咳博德特氏菌具有杀菌作用，其效价与其 ELISA 值相关。载体蛋白计划是经过基因改造的百日咳毒素。此类结合物易于制备，稳定，并且应该既可以提高当前疫苗诱导的百日咳抗体所引起的免疫水平和持续时间，又可以减少百日咳博德特氏菌的循环。
