Rickard M D
CSIRO Division of Animal Health, Parkville, Victoria, Australia.
Southeast Asian J Trop Med Public Health. 1991 Dec;22 Suppl:287-90.
Studies over the past 20 years have clearly shown the potential for developing vaccines against larval cestode infections of man and animals. The important larval cestode infections of man (Echinococcus granulosus--hydatidosis: Taenia solium--cysticercosis) involve domesticated animals as intermediate hosts in their natural life-cycles. These animals develop strong immunity against reinfection, and immunity can be artificially induced by vaccination with oncosphere antigens. A major stumbling block in developing commercial vaccines against cestodes has been the difficulty in obtaining adequate supplies of these antigens. Recent studies with Taenia ovis, a larval cestode causing cysticercosis in sheep, have demonstrated the feasibility of developing commercial vaccines against cestodes using recombinant DNA technology. A cDNA library prepared using mRNA obtained from T. ovis oncospheres was used to isolate a clone which expressed T. ovis polypeptide antigen 45W as a fusion protein with Schistosoma japonicum glutathione S-transferase (GST-45W). GST-45W gave up to 94% protection against challenge infection when used to vaccinate sheep with saponin as adjuvant. The vaccine antigen was shown by SDS PAGE to be unstable, a major disadvantage in subsequent attempts to obtain high yields of antigen for commercial production. The fusion protein has now been stabilized by reducing the size of GST-45W cDNA through deleting 19 carboxyl terminal hydropathic acids, and the resultant fusion protein GST-45W (B/X) was highly host-protective. Another experiment showed that the 45W T. ovis polypeptide cleaved enzymatically from GST-45W was still host-protective, suggesting that GST had no influence on the immunogenicity of GST-45W fusion protein.(ABSTRACT TRUNCATED AT 250 WORDS)
过去20年的研究清楚地表明了开发针对人和动物幼虫绦虫感染疫苗的潜力。人类重要的幼虫绦虫感染(细粒棘球绦虫——包虫病;猪带绦虫——囊尾蚴病)在其自然生命周期中涉及家畜作为中间宿主。这些动物对再次感染产生强大的免疫力,并且可以通过用六钩蚴抗原进行疫苗接种来人工诱导免疫力。开发针对绦虫的商业疫苗的一个主要障碍是难以获得足够数量的这些抗原。最近对绵羊带绦虫(一种导致绵羊囊尾蚴病的幼虫绦虫)的研究表明,使用重组DNA技术开发针对绦虫的商业疫苗是可行的。使用从绵羊带绦虫六钩蚴获得的mRNA制备的cDNA文库用于分离一个克隆,该克隆表达绵羊带绦虫多肽抗原45W,作为与日本血吸虫谷胱甘肽S-转移酶(GST-45W)的融合蛋白。当用皂苷作为佐剂用于给绵羊接种疫苗时,GST-45W对攻击感染提供高达94%的保护。通过SDS-PAGE显示疫苗抗原不稳定,这是随后为商业生产获得高产率抗原的尝试中的一个主要缺点。现在通过删除19个羧基末端疏水氨基酸来减小GST-45W cDNA的大小,从而使融合蛋白稳定,并且所得的融合蛋白GST-45W(B/X)具有高度的宿主保护作用。另一项实验表明,从GST-45W酶切得到的45W绵羊带绦虫多肽仍然具有宿主保护作用,这表明GST对GST-45W融合蛋白的免疫原性没有影响。(摘要截短至250字)