Eyles J E, Sharp G J, Williamson E D, Spiers I D, Alpar H O
Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK.
Vaccine. 1998 Apr;16(7):698-707. doi: 10.1016/s0264-410x(97)00249-1.
Equivocal doses of soluble, or high molecular weight poly (lactic acid) microsphere co-encapsulated, F1 and V subunit antigens of Yersinia pestis were used to immunize mice intra-nasally. Animals were dosed on day 1 and 7 with 2.724 micrograms V plus 0.956 micrograms F1. Co-encapsulated antigens induced superior systemic and mucosal immunity in comparison with free F1 and V. All of the mice immunized with soluble antigens died shortly after an aerosol challenge consisting of 1 x 10(5) colony-forming units of plague bacteria. In contrast, 66% of the co-encapsulated subunit vaccinees survived this lethal challenge. Humoral immunity to plague was improved further, resulting in 80% protection from challenge, if a relatively high dose (10 micrograms) of cholera toxin B subunit was added to the microsphere suspension prior to intra-nasal delivery. Significantly, by adding 10 micrograms cholera toxin B subunit to the free antigen solution, a 100% post-challenge survival rate was attained. We conclude that in this animal model of pneumonic plague, intra-nasal administration of microgram quantities of Yersinia pestis subunits confers protective immunity, provided the vaccines are microencapsulated or admixed with a strong mucosal adjuvant, such as the cholera toxin B subunit.
使用等量的可溶性或高分子量聚（乳酸）微球共包封的鼠疫耶尔森菌F1和V亚单位抗原经鼻内免疫小鼠。在第1天和第7天给动物注射2.724微克V加0.956微克F1。与游离的F1和V相比，共包封的抗原诱导了更强的全身和黏膜免疫。所有用可溶性抗原免疫的小鼠在接受由1×10⁵个鼠疫菌落形成单位组成的气溶胶攻击后不久死亡。相比之下，66%的共包封亚单位疫苗接种小鼠在这种致死性攻击中存活下来。如果在经鼻给药前向微球悬液中加入相对高剂量（10微克）的霍乱毒素B亚单位，对鼠疫的体液免疫会进一步提高，从而使80%的小鼠免受攻击。值得注意的是，通过向游离抗原溶液中加入10微克霍乱毒素B亚单位，攻击后的存活率达到了100%。我们得出结论，在这种肺鼠疫动物模型中，经鼻给予微克量的鼠疫耶尔森菌亚单位可赋予保护性免疫，前提是疫苗被微囊化或与强黏膜佐剂如霍乱毒素B亚单位混合。
