Sack Brandon, Kappe Stefan H I, Sather D Noah
a Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute) , Seattle , WA , USA.
b Department of Global Health , University of Washington , Seattle , WA , USA.
Expert Rev Vaccines. 2017 May;16(5):403-414. doi: 10.1080/14760584.2017.1295853. Epub 2017 Mar 1.
An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.
一种有效的疟疾疫苗将被视为现代医学的一个里程碑，但迄今为止，研发工作仍未成功。这可归因于疟原虫极其复杂，其具有多阶段生命周期、高基因组复杂性以及寄生虫复杂的免疫逃避措施，尤其是在致病性血液阶段感染期间的抗原变异。然而，寄生虫的前红细胞期（PE）早期感染形式表现出相对不变的蛋白质组，并且由于它们提供了免疫系统攻击的多个靶点，因此是有吸引力的疫苗靶点。涵盖领域：我们涵盖了基于抗体的有效PE疫苗开发的现状和障碍，包括当前的候选疫苗、有限的生物学知识、遗传异质性、寄生虫复杂性、欠佳的临床前模型以及早期临床模型的作用。专家评论：PE疫苗需要引发广泛而持久的免疫力以预防感染。如果将近期在研究寄生虫感染生物学、合理的疫苗选择和设计以及佐剂配方方面的创新以协同和多管齐下的方式结合起来，这是可以实现的。改进的临床前检测以及在受控人类疟疾感染试验中对候选疫苗的迭代测试将进一步加速这一努力。
