Genton Blaise, Reed Zarifah H
Ifakara Health Research and Development Center, Dar Es Salaam, Tanzania.
Curr Opin Infect Dis. 2007 Oct;20(5):467-75. doi: 10.1097/QCO.0b013e3282dd7a29.
The aim of this article is to highlight the challenges that researchers face in the development of asexual blood-stage vaccines, and the progress made recently towards achieving the goal of a successful candidate to reduce morbidity.
There is good rationale to support the development of blood-stage malaria vaccines, the most promising being the demonstration that nonimmune volunteers repeatedly challenged and cured with blood-stage parasites developed immunity to subsequent challenge as well as the demonstration of the efficacy of the first asexual blood-stage vaccine tested in a malaria endemic area (combination B) to reduce parasite density in children. The selective pressure induced by this vaccine and the accumulating evidence of extensive antigenic diversity of blood-stage proteins pose a difficult challenge to vaccine researchers. Numerous clinical trials, both in nonendemic and endemic areas, are being conducted with different antigens, different allelic types and different protein fragments.
Considerable efforts and funding are available to shift from laboratory experiments to field trials. Field trials remain the definitive method to assess the real impact of different vaccines in the target populations. More rigorous side-by-side comparisons are needed between the different vaccines using standardized in-vitro and in-vivo testing, so that the most promising candidates will be selected for further development.
本文旨在强调研究人员在开发无性血液期疟疾疫苗过程中面临的挑战,以及近期在实现成功候选疫苗以降低发病率目标方面取得的进展。
有充分的理由支持开发血液期疟疾疫苗,最有前景的是以下两点:一是证明非免疫志愿者经血液期寄生虫反复攻击并治愈后,对后续攻击产生了免疫力;二是在疟疾流行地区测试的第一种无性血液期疫苗(组合B)显示出降低儿童寄生虫密度的功效。这种疫苗所诱导的选择压力以及血液期蛋白质广泛抗原多样性的越来越多的证据,给疫苗研究人员带来了艰巨的挑战。在非流行地区和流行地区都正在针对不同抗原、不同等位基因类型和不同蛋白质片段开展大量临床试验。
为了从实验室实验转向现场试验,已经付出了巨大努力并投入了大量资金。现场试验仍然是评估不同疫苗对目标人群实际影响的决定性方法。需要使用标准化的体外和体内测试对不同疫苗进行更严格的并行比较,以便选出最有前景的候选疫苗进行进一步开发。