Winter J A, Davies O R, Brown A P, Garnett M C, Stolnik S, Pritchard D I
University of Nottingham, School of Pharmacy, University Park, Nottingham, NG7 2RD, UK.
Parasite Immunol. 2005 Apr;27(4):139-46. doi: 10.1111/j.1365-3024.2005.00756.x.
A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm-induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43-49% fewer worms in their lungs, compared to non-vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 microg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti-calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin-loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.
迫切需要一种针对美洲板口线虫的疫苗，以降低流行地区钩虫引起的发病率。在本研究中，已在小鼠身上测试了一种被提名的疫苗候选物——重组钩虫钙网蛋白。在用感染性钩虫幼虫进行攻击感染后，与未接种疫苗的对照组相比，接种钙网蛋白的小鼠肺部的蠕虫数量减少了43%至49%。在腹腔注射三剂15微克抗原且无佐剂的情况下达到了这些保护水平。抗原也被包裹在聚乳酸-羟基乙酸共聚物（PLG）微粒中。包裹的钙网蛋白比游离抗原诱导出更高水平的抗钙网蛋白IgG1，但未能诱导保护性免疫。游离钙网蛋白诱导的保护作用与低水平的血清IgE和中度肺嗜酸性粒细胞增多有关，而注射负载钙网蛋白的微粒则与高水平的血清IgE和更高的肺嗜酸性粒细胞活性有关，这表明经典的Th2表型可能并不总是与保护性免疫相关，尽管是在实验性板口线虫病中。
