Veterinary Parasitology Group, Liverpool School of Tropical Medicine and Faculty of Veterinary Science, University of Liverpool, Liverpool, United Kingdom.
PLoS Negl Trop Dis. 2009 Nov 10;3(11):e544. doi: 10.1371/journal.pntd.0000544.
Human onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is controlled almost exclusively by the drug ivermectin, which prevents pathology by targeting the microfilariae. However, this reliance on a single control tool has led to interest in vaccination as a potentially complementary strategy. Here, we describe the results of a trial in West Africa to evaluate a multivalent, subunit vaccine for onchocerciasis in the naturally evolved host-parasite relationship of Onchocerca ochengi in cattle. Naïve calves, reared in fly-proof accommodation, were immunised with eight recombinant antigens of O. ochengi, administered separately with either Freund's adjuvant or alum. The selected antigens were orthologues of O. volvulus recombinant proteins that had previously been shown to confer protection against filarial larvae in rodent models and, in some cases, were recognised by serum antibodies from putatively immune humans. The vaccine was highly immunogenic, eliciting a mixed IgG isotype response. Four weeks after the final immunisation, vaccinated and adjuvant-treated control calves were exposed to natural parasite transmission by the blackfly vectors in an area of Cameroon hyperendemic for O. ochengi. After 22 months, all the control animals had patent infections (i.e., microfilaridermia), compared with only 58% of vaccinated cattle (P = 0.015). This study indicates that vaccination to prevent patent infection may be an achievable goal in onchocerciasis, reducing both the pathology and transmissibility of the infection. The cattle model has also demonstrated its utility for preclinical vaccine discovery, although much research will be required to achieve the requisite target product profile of a clinical candidate.
人类盘尾丝虫病是由丝虫科线虫盘尾丝虫引起的，几乎完全由伊维菌素这种药物来控制，该药通过靶向微丝蚴来预防疾病。然而，对单一控制工具的这种依赖，使得人们对疫苗作为一种潜在的补充策略产生了兴趣。在这里，我们描述了在西非进行的一项试验结果，该试验评估了一种针对盘尾丝虫的多价亚单位疫苗，在盘尾丝虫与牛这种自然进化的宿主-寄生虫关系中，该疫苗针对的是盘尾丝虫的微丝蚴。在无蝇的住所中饲养的新生小牛用 8 种盘尾丝虫重组抗原进行免疫，单独用弗氏佐剂或明矾佐剂进行给药。所选抗原是盘尾丝虫重组蛋白的同源物，这些重组蛋白先前已被证明在啮齿动物模型中能对丝虫幼虫提供保护，在某些情况下，还能被来自疑似免疫人群的血清抗体识别。该疫苗具有高度免疫原性，能引起混合 IgG 同型反应。最后一次免疫 4 周后，用黑蝇媒介在喀麦隆高度流行区对接种疫苗和佐剂处理的对照小牛进行自然寄生虫传播的暴露。22 个月后，所有对照动物都出现了显性感染（即微丝蚴血症），而接种疫苗的牛只有 58%（P = 0.015）。这项研究表明，预防显性感染的疫苗接种可能是盘尾丝虫病的一个可行目标，可以降低感染的病理和传染性。牛模型还证明了它在临床前疫苗发现中的实用性，尽管要实现临床候选疫苗的必要目标产品特征还需要进行大量研究。
