Optimising a High Efficacy Plasmodium vivax Malaria Vaccine (OptiViVax)

间日疟原虫是分布最广泛的人类疟疾，在非洲、南美洲、大洋洲和亚洲有25亿人面临风险。修订后的《到2030年疟疾疫苗技术路线图》认识到间日疟的严重性，呼吁采取疫苗干预措施，在两年内达到75%的效果，现在与恶性疟原虫同等权重。然而，如果要实现这一雄心，迫切需要新的和创新的方法来加快下一代疫苗的研究和开发，而为数不多的已知候选抗原需要进行早期临床评估。在这里，我们建立在欧洲最近率先在间日疟原虫疫苗研究方面取得的令人兴奋的突破，包括用于功能分析开发的新的转基因寄生虫技术，以及生产可安全用于受控人类疟疾感染(CHMI)临床模型的寄生虫克隆。OptiViVax的目标将围绕寄生虫的生命周期整合雄心勃勃的多学科科学和临床方法，并将利用我们对间日疟原虫免疫生物学的日益增长的知识来进一步开发效率更高的下一代疫苗。我们将通过反向疫苗学使准备用于临床测试的新抗原组合多样化，并通过使用可持续和改进的GMP生物制造技术开发的新平台和佐剂使其交付多样化。同时，将首次使用创新设计的临床研究和CHMI模型对已知主要抗原的效力进行基准测试，使这些主要候选疫苗为未来的现场试验做好准备。改进的临床前功能分析，使用最先进的转基因寄生虫系，也将允许破译抗体介导的保护机制。新的功能分析和人类挑战模型的可获得性将为临床疫苗社区、政策制定者、资助者和监管机构做出明智决策的未来框架奠定基础。

Plasmodium vivax is the most widespread human malaria with 2.5 billion people living at risk in Africa, South America, Oceania and Asia. The revised Malaria Vaccine Technology Roadmap to 2030 recognises the severity of P. vivax malaria, calling for a vaccine intervention to achieve 75% efficacy over two years, now equally weighted with P. falciparum. However, if this ambition is to be realised, new and innovative approaches are urgently required to accelerate next-generation vaccine research and development, whilst the few known candidate antigens need to undergo early-phase clinical assessment. Here, we build on exciting breakthroughs in P. vivax vaccine research, recently pioneered in Europe, including new transgenic parasite technologies for functional assay development and production of a parasite clone that is safe for use in controlled human malaria infection (CHMI) clinical models. The Objectives of OptiViVax will integrate ambitious multi-disciplinary scientific and clinical approaches around the parasite’s lifecycle and will use our increased knowledge of P. vivax immuno-biology to further develop next-generation vaccines with improved efficacy. We will diversify the portfolio of new antigens ready for clinical testing by reverse vaccinology and diversify their delivery with new platforms and adjuvants developed using sustainable and improved GMP bio-manufacturing know-how. In parallel, the efficacy of known leading antigens will be benchmarked for the first time using innovative design of clinical studies and CHMI models making these lead candidate vaccines ready for future field trials. Improved preclinical functional assays, using state-of-the-art transgenic parasite lines, will also allow for mechanisms of antibody-mediated protection to be deciphered. The availability of new functional assays and human challenge models will underpin the future framework for informed decision making by the clinical vaccine community, policy makers, funders and regulators.