Giersing Birgitte K, Dubovsky Filip, Saul Allan, Denamur Francoise, Minor Philip, Meade Bruce
PATH Malaria Vaccine Initiative (MVI), Bethesda, MD 20814, USA.
Vaccine. 2006 May 15;24(20):4264-70. doi: 10.1016/j.vaccine.2006.01.005.
Many licensed vaccines are composed of live, attenuated or inactivated whole-cell microorganisms, or they comprise purified components from whole-cell extracts or culture supernatants. For some diseases, pathology is fairly well understood, and there may be known correlates of protection that provide obvious parameters for assessment of vaccine potency. However, this is not always the case, and some effective vaccines are routinely used even though the mechanisms or correlates of protection are unknown. Some more modern vaccine approaches employ purified recombinant proteins, based on molecules that appear on the surface of the pathogen. This is one of the strategies that has been adopted in the quest to develop a malaria vaccine. Use of these parasite antigens as vaccine candidates is supported by substantial epidemiological data, and some have demonstrated the ability to elicit protective responses in animal models of malaria infection. However, there is as yet no immunological correlate of protection and no functional assays or animal models that have demonstrated the ability to predict efficacy in humans. There is little precedence for the most appropriate and practical method for assessing potency of vaccines based on these recombinant molecules for malaria vaccines. This is likely because the majority of malaria vaccine candidates have only recently entered clinical evaluation. The PATH Malaria Vaccine Initiative (MVI) convened a panel with expertise in potency assay design from industry, governmental institutions, and regulatory bodies to discuss and review the rationale, available methods, and best approaches for assessing the potency of recombinant proteins, specifically for their use as malarial vaccines. The aim of this meeting was to produce a discussion document on the practical potency assessment of recombinant protein malaria vaccines, focusing on early phase potency assay development.
许多获得许可的疫苗由减毒活疫苗或灭活全细胞微生物组成，或者包含从全细胞提取物或培养上清液中纯化的成分。对于某些疾病，其病理情况已相当清楚，可能存在已知的保护相关指标，为评估疫苗效力提供明显参数。然而，情况并非总是如此，一些有效的疫苗即使其保护机制或相关指标尚不清楚，仍被常规使用。一些更现代的疫苗方法采用基于病原体表面出现的分子的纯化重组蛋白。这是在研发疟疾疫苗过程中所采用的策略之一。大量流行病学数据支持将这些寄生虫抗原用作疫苗候选物，并且其中一些已证明能够在疟疾感染动物模型中引发保护性反应。然而，目前尚无保护的免疫学相关指标，也没有功能测定方法或动物模型能够证明可预测对人类的疗效。对于基于这些重组分子的疟疾疫苗，评估其效力的最合适和实用方法几乎没有先例。这可能是因为大多数疟疾疫苗候选物直到最近才进入临床评估阶段。PATH疟疾疫苗倡议组织（MVI）召集了一个由来自行业机构、政府机构和监管机构的效力测定设计专家组成的小组，讨论和审查评估重组蛋白效力的基本原理、可用方法和最佳途径，特别是将其用作疟疾疫苗的情况。本次会议的目的是编写一份关于重组蛋白疟疾疫苗实际效力评估的讨论文件，重点关注早期效力测定方法的开发。
