Burnet Institute, Melbourne, Vic., Australia.
Central Clinical School, Monash University, Melbourne, Vic., Australia.
Immunol Rev. 2020 Jan;293(1):38-56. doi: 10.1111/imr.12802. Epub 2019 Sep 26.
Developing efficacious vaccines for human malaria caused by Plasmodium falciparum is a major global health priority, although this has proven to be immensely challenging over the decades. One major hindrance is the incomplete understanding of specific immune responses that confer protection against disease and/or infection. While antibodies to play a crucial role in malaria immunity, the functional mechanisms of these antibodies remain unclear as most research has primarily focused on the direct inhibitory or neutralizing activity of antibodies. Recently, there is a growing body of evidence that antibodies can also mediate effector functions through activating the complement system against multiple developmental stages of the parasite life cycle. These antibody-complement interactions can have detrimental consequences to parasite function and viability, and have been significantly associated with protection against clinical malaria in naturally acquired immunity, and emerging findings suggest these mechanisms could contribute to vaccine-induced immunity. In order to develop highly efficacious vaccines, strategies are needed that prioritize the induction of antibodies with enhanced functional activity, including the ability to activate complement. Here we review the role of complement in acquired immunity to malaria, and provide insights into how this knowledge could be used to harness complement in malaria vaccine development.
开发针对恶性疟原虫引起的人类疟疾的有效疫苗是全球主要的卫生重点，但几十年来这一目标一直难以实现。主要障碍之一是对能预防疾病和/或感染的特定免疫反应了解不完整。抗体在疟疾免疫中发挥着关键作用，但这些抗体的功能机制尚不清楚，因为大多数研究主要集中在抗体的直接抑制或中和活性上。最近，越来越多的证据表明，抗体还可以通过激活补体系统来针对寄生虫生命周期的多个发育阶段来发挥效应功能。这些抗体-补体相互作用可能对寄生虫的功能和生存能力产生不利影响，并与自然获得性免疫中对临床疟疾的保护显著相关，新出现的研究结果表明，这些机制可能有助于疫苗诱导的免疫。为了开发高效疫苗，需要制定策略，优先诱导具有增强功能活性的抗体，包括激活补体的能力。在这里，我们回顾了补体在疟疾获得性免疫中的作用，并提供了如何利用这方面的知识来开发疟疾疫苗的见解。
