Levenson V I, Egorova T P, Belkin Z P, Fedosova V G, Subbotina J L, Rukhadze E Z, Dzhikidze E K, Stassilevich Z K
Laboratory of Subcellular Bacterial Structures, Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology, Moscow, USSR.
Infect Immun. 1991 Oct;59(10):3610-8. doi: 10.1128/iai.59.10.3610-3618.1991.
A parenteral Shigella ribosomal vaccine (SRV) was investigated in animals for safety, antibody-inducing capacity, and protective activity. Ribosomal preparations from a Shigella sonnei phase I avirulent strain were obtained and shown to possess chemical, sedimentation, and other properties typical of bacterial ribosomes. No endotoxin contamination was revealed by a ketodeoxyoctonate assay, although the presence of some kind of O antigen was evidenced by serological findings and the high activity of SRV in inducing the O-antibody response and immunological memory in animals. SRV was nontoxic in mice, guinea pigs, and monkeys and induced no local reactions when injected subcutaneously in reasonable doses. Significant protection against a local Shigella infection (Sereny test) was seen in guinea pigs injected with SRV (efficiency index, about 60%) and the specificity of the protection was evident from cross-challenge experiments. The protective efficiency of SRV was especially high in rhesus monkeys challenged orally with virulent Shigella cells (89%, as calculated from the summarized data of several experiments in 71 animals). Protection in monkeys was long lasting and could be demonstrated several months after injection of SRV. An inexpensive technique can be used for the production of SRV on a large scale. The high immunogenicity of SRV is discussed in terms of the amplifying effect of the ribosome, which serves as a delivery system for polysaccharide O antigen. Further study of SRV as a candidate vaccine for humans seems justified by the data obtained.
一种肠道外志贺氏菌核糖体疫苗(SRV)在动物身上进行了安全性、抗体诱导能力和保护活性的研究。从宋内志贺氏菌I期无毒菌株中获得了核糖体制剂,并证明其具有细菌核糖体典型的化学、沉降和其他特性。尽管血清学结果证明存在某种O抗原,并且SRV在诱导动物O抗体反应和免疫记忆方面具有高活性,但通过酮脱氧辛糖酸测定未发现内毒素污染。SRV对小鼠、豚鼠和猴子无毒,以合理剂量皮下注射时不会引起局部反应。在注射SRV的豚鼠中观察到对局部志贺氏菌感染(塞雷尼试验)有显著保护作用(效率指数约为60%),并且交叉攻击实验证明了保护的特异性。在用有毒力的志贺氏菌细胞口服攻击的恒河猴中,SRV的保护效率特别高(根据71只动物的多个实验汇总数据计算为89%)。对猴子的保护作用持久,在注射SRV几个月后仍可证明。一种廉价的技术可用于大规模生产SRV。根据核糖体作为多糖O抗原递送系统的放大作用,讨论了SRV的高免疫原性。根据所获得的数据,进一步研究SRV作为人类候选疫苗似乎是合理的。