Shirley Martin W, Smith Adrian L, Tomley Fiona M
Institute for Animal Health, Compton Laboratory, Compton Nr Newbury, Berks RG20 7NN, UK.
Adv Parasitol. 2005;60:285-330. doi: 10.1016/S0065-308X(05)60005-X.
Studies on the biology of the avian species of Eimeria are currently benefiting from the availability of a comprehensive sequence for the nuclear genome of Eimeria tenella. Allied to some recent advances in transgenic technologies and genetic approaches to identify protective antigens, some elements are now being assembled that should be helpful for the development of a new generation of vaccines. In the meantime, control of avian coccidiosis by vaccination represents a major success in the fight against infections caused by parasitic protozoa. Live vaccines that comprise defined populations of oocysts are used routinely and this form of vaccination is based upon the long-established fact that chickens infected with coccidial parasites rapidly develop protective immunity against challenge infections with the same species. Populations of wild-type Eimeria parasites were the basis of the first live vaccines introduced around 50 years ago and the more recent introduction of safer, live-attenuated, vaccines has had a significant impact on coccidiosis control in many areas of the world. In Europe the introduction of vaccination has coincided with declining drug efficacy (on account of drug resistance) and increasing concerns by consumers about the inclusion of in-feed medication and prospects for drug residues in meat. The use of attenuated vaccines throughout the world has also stimulated a greater interest in the vaccines that comprise wild-type parasites and, during the past 3 years worldwide, around 3x10(9) doses of each type of vaccine have been used. The need for only small numbers of live parasites to induce effective protective immunity and the recognition that Eimeria spp. are generally very potent immunogens has stimulated efforts to develop other types of vaccines. None has succeeded except for the licensing, within several countries in 2002, of a vaccine (CoxAbic vaccine; Abic, Israel) that protects via the maternal transfer of immunoglobulin to the young chick. Building on the success of viral vaccines that are delivered via the embryonating egg, an in ovo coccidiosis vaccine (Inovocox, Embrex Inc.) is currently in development. Following successful field trials in 2001, the product will be ready for Food and Drug Administration approval in 2005 and a manufacturing plant will begin production for sale in late 2005. Limited progress has been achieved towards the development of subunit or recombinant vaccines. No products are available and studies to identify potential antigens remain compromised by an absence of effective in vitro assays that correlate with the induction of protective immunity in the host. To date, only a relatively small portfolio of molecules has been evaluated for an ability to induce protection in vivo. Although Eimeria are effective immunogens, it is probable that to date none of the antigens that induce potent protective immune responses during the course of natural infection has been isolated.
目前,艾美耳球虫属禽类物种的生物学研究受益于柔嫩艾美耳球虫核基因组完整序列的可得性。与转基因技术和鉴定保护性抗原的遗传方法方面的一些最新进展相结合,现在正在整合一些要素,这应该有助于新一代疫苗的开发。与此同时,通过疫苗接种控制禽球虫病是对抗寄生原生动物感染斗争中的一项重大成功。包含特定卵囊群体的活疫苗被常规使用,这种疫苗接种形式基于一个长期确立的事实,即感染球虫寄生虫的鸡会迅速产生针对同一物种攻击感染的保护性免疫力。野生型艾美耳球虫寄生虫群体是大约50年前推出的首批活疫苗的基础,最近推出的更安全的减毒活疫苗对世界许多地区的球虫病控制产生了重大影响。在欧洲,疫苗接种的引入恰逢药物疗效下降(由于耐药性)以及消费者对饲料中添加药物和肉类中药物残留前景的担忧增加。全世界减毒疫苗的使用也激发了对包含野生型寄生虫的疫苗的更大兴趣,在过去3年里,全球每年每种类型的疫苗使用量约为3×10⁹剂。只需少量活寄生虫就能诱导有效的保护性免疫力,以及认识到艾美耳球虫属通常是非常有效的免疫原,这激发了开发其他类型疫苗的努力。除了2002年在几个国家批准了一种通过母体向幼雏转移免疫球蛋白来提供保护的疫苗(CoxAbic疫苗;以色列Abic公司)外,其他努力均未成功。基于通过胚胎蛋递送的病毒疫苗的成功经验,一种卵内球虫病疫苗(Inovocox,Embrex公司)目前正在研发中。在2001年成功进行田间试验后,该产品将于2005年准备好提交美国食品药品监督管理局批准,一家生产工厂将于2005年底开始生产销售。亚单位疫苗或重组疫苗开发方面进展有限。尚无产品上市,由于缺乏与宿主中保护性免疫诱导相关的有效体外试验,鉴定潜在抗原的研究仍然受到影响。迄今为止,只有相对较少的一组分子被评估了在体内诱导保护的能力。尽管艾美耳球虫是有效的免疫原,但很可能迄今为止尚未分离出在自然感染过程中诱导有效保护性免疫反应的任何抗原。