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首页> 外文期刊>Infection and immunity >Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine
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Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

机译：皮肤免疫接种减毒的伯克霍尔德氏假小肠疫苗后的免疫保护相关性

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Infections with the Gram-negative bacterium Burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with B. pseudomallei. At present, our understanding of what constitutes effective protective immunity against B. pseudomallei infection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acute B. pseudomallei infection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excluded purM deletion mutant of B. pseudomallei (strain Bp82) and then subjected to intranasal challenge with virulent B. pseudomallei strain 1026b. Immunization with Bp82 generated significant protection from challenge with B. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuated Burkholderia vaccine strain was dependent primarily on generation of effective humoral immune responses.
机译：革兰氏阴性细菌假苹果伯克霍尔德氏菌（类胡oid病）的感染与高死亡率有关，目前尚无批准的疫苗可预防人类类胡oid病的发展。感染的患者对再感染也没有形成保护性免疫力，有些人会发展成假性双歧杆菌的慢性亚临床感染。目前，我们对什么构成对假苹果芽孢杆菌感染的有效保护性免疫的理解仍不完全。因此，我们进行了一项研究，以阐明疫苗诱导的针对急性假芽孢杆菌感染的保护性免疫的免疫相关性。 BALB / c和C57BL / 6小鼠皮下注射高度减毒，选择剂除外的拟假芽孢杆菌purM缺失突变体（菌株Bp82）进行皮下免疫，然后用有毒的假拟芽孢杆菌1026b进行鼻内攻击。 Bp82免疫产生了抵抗假假单胞菌攻击的显着保护作用，并且该保护作用与免疫小鼠肺，肝和脾脏细菌负荷的显着降低有关。体液免疫对于疫苗诱导的保护至关重要，因为缺乏B细胞的小鼠没有受到免疫保护，而接种Bp82的小鼠的血清可以将部分保护转移给未接种的动物。相反，发现疫苗诱导的保护性免疫独立于CD4和CD8 T细胞。追踪研究表明，Bp82疫苗株主要通过引流疫苗的淋巴结中的中性粒细胞以及较少数量的树突状细胞（DC）和单核细胞摄取。我们得出结论，用减毒活的伯克霍尔德氏菌疫苗株进行皮肤免疫后的保护主要取决于有效体液免疫反应的产生。

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