Linde K, Beer J, Bondarenko V
Institute of Medical Microbiology and Epidemiology, Karl Marx University, Leipzig, GDR.
Vaccine. 1990 Jun;8(3):278-82. doi: 10.1016/0264-410x(90)90058-t.
Mutants optimally attenuated for highly susceptible hosts and protecting after a single oral vaccination are often overattenuated for host species being less susceptible. Therefore, to select vaccine strains optimally attenuated for the particular host species it is essential that a range of mutants with graded levels of attenuation be provided so as to permit lesser susceptibility to be compensated for by a correspondingly lower level of attenuation. This, while guaranteeing the stability through two-marker or multi-marker attenuation, can be suitably accomplished by slightly to moderately virulence-reducing mutations. Aspartic acid auxotrophy and, in particular, 'metabolic drift' mutations, possibly by additionally incorporating antiepidemic markers, are adopted for the mouse model to demonstrate stepwise production of S. typhimurium and S. typhi vaccine candidate strains with graded attenuation or any level of attenuation desirable. It is emphasized that this basic approach is relevant to practice.
对于高度易感宿主而言，经最佳减毒且单次口服疫苗接种后具有保护作用的突变体，对于较不易感的宿主物种往往减毒过度。因此，为了选择针对特定宿主物种最佳减毒的疫苗株，提供一系列具有不同程度减毒水平的突变体至关重要，以便通过相应较低的减毒水平来弥补较低的易感性。这在通过双标记或多标记减毒保证稳定性的同时，可以通过轻微至中度降低毒力的突变来适当地实现。在小鼠模型中采用天冬氨酸营养缺陷型，特别是“代谢漂移”突变，可能还纳入抗流行标记，以逐步生产具有不同程度减毒或任何所需减毒水平的鼠伤寒沙门氏菌和伤寒沙门氏菌候选疫苗株。需要强调的是，这种基本方法与实际应用相关。
