PATH Malaria Vaccine Initiative, Washington, DC 20001-2621, USA.
Vaccine. 2013 Apr 18;31 Suppl 2:B233-43. doi: 10.1016/j.vaccine.2013.02.040.
While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document.
尽管最近在通过其他干预措施降低疟疾死亡率方面取得了进展，但仍迫切需要疫苗来进一步降低临床疾病的发病率，包括在妊娠期间，并通过阻断寄生虫传播来提供“群体保护”。最具临床前景的候选疫苗 RTS,S 目前正在非洲 8 个国家的 13 个临床点对 13 岁以下的非洲儿童进行 3 期评估。在接种后的 12 个月内，RTS,S 使 5-17 个月大的儿童发生临床疟疾病的保护率约为 50%，在与扩大免疫规划（EPI）疫苗联合使用时，6-12 周大的儿童的保护率约为 30%。开发更高效的疫苗来预防疟原虫和间日疟原虫引起的临床疾病，以及开发通过诱导阻断疟疾寄生虫传播的免疫来支持消除努力的疫苗，是优先事项。疟疾疫苗开发的一些关键障碍包括：缺乏经过充分表征的目标免疫原，以及缺乏明确的保护相关性，以使针对疟原虫和间日疟原虫生命周期所有阶段的疫苗开发成为可能；安全有效的输送系统数量有限，包括佐剂，这些系统可以通过抗体、CD4+和/或 CD8+T 细胞反应来诱导强烈的、持久的保护性免疫；以及对于旨在通过针对有性阶段和/或蚊子抗原来提供“群体保护”的疫苗，缺乏使用非传统终点来获得明确的临床和监管途径的许可。本文提出了克服这些以及其他关键挑战的建议。
