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佐剂对非活性血吸虫病疫苗诱导保护性免疫的影响

The influence of adjuvant on induction of protective immunity by a non-living vaccine against schistosomiasis.

作者信息

James S L, Pearce E J

机构信息

Department of Medicine, George Washington University Medical Center, Washington, DC 20037.

出版信息

J Immunol. 1988 Apr 15;140(8):2753-9.

PMID:3128608
Abstract

Mice were protected against subsequent infection with Schistosoma mansoni by intradermal or s.c. vaccination with killed schistosomula or soluble parasite extracts and bacillus Calmette-Guérin (BCG). Treatment with i.p. immunization was somewhat less effective, whereas i.m. vaccination failed to elicit protective immunity. The level of resistance induced by intradermal immunization was influenced by the strain of BCG used, and isolated BCG cell walls did not reliably substitute for whole BCG organisms as adjuvant. Bordetella pertussis vaccine and saponin were also able to function as adjuvants for protective immunity in this model, whereas other immunopotentiators including Corynebacterium parvum and aluminum hydroxide were ineffective. No correlation between resistance to challenge infection and antibody levels was detected. Animals immunized intradermally using either protective or non-protective adjuvants all showed minimal humoral reactivity against schistosomulum surface Ag but strong IgG response to soluble parasite components including paramyosin, which is the major serologically recognized Ag in mice vaccinated intradermally with schistosome Ag plus BCG and is protective in this model. In contrast, a strong correlation was observed between resistance and Ag-specific cell-mediated reactivity, including IFN production by T lymphocytes in vitro and macrophage activation in vivo. These results further substantiate the hypothesis that protection in this model is based on cell-mediated immune effector mechanisms. Moreover, they may be of general relevance in the design of vaccination protocols using other Ag or against other infectious agents.

摘要

通过用灭活的血吸虫幼虫或可溶性寄生虫提取物以及卡介苗(BCG)进行皮内或皮下接种,小鼠可免受随后曼氏血吸虫的感染。腹腔内免疫治疗的效果稍差,而肌肉内接种未能引发保护性免疫。皮内免疫诱导的抵抗力水平受所用卡介苗菌株的影响,分离的卡介苗细胞壁不能可靠地替代完整的卡介苗生物体作为佐剂。百日咳博德特氏菌疫苗和皂苷在此模型中也能够作为保护性免疫的佐剂发挥作用,而其他免疫增强剂,包括短小棒状杆菌和氢氧化铝则无效。未检测到对攻击感染的抵抗力与抗体水平之间的相关性。使用保护性或非保护性佐剂进行皮内免疫的动物,均对血吸虫幼虫表面抗原表现出最小的体液反应性,但对包括副肌球蛋白在内的可溶性寄生虫成分表现出强烈的IgG反应,副肌球蛋白是在皮内接种血吸虫抗原加卡介苗的小鼠中主要的血清学识别抗原,并且在此模型中具有保护作用。相比之下,观察到抵抗力与抗原特异性细胞介导的反应性之间存在强烈相关性,包括体外T淋巴细胞产生的干扰素和体内巨噬细胞的激活。这些结果进一步证实了该模型中的保护作用基于细胞介导的免疫效应机制这一假设。此外,它们可能在使用其他抗原或针对其他传染原的疫苗接种方案设计中具有普遍相关性。

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