Optimising a High Efficacy Plasmodium vivax Malaria Vaccine (OptiViVax)

间日疟原虫是传播最广的人类疟疾，在非洲、南美洲、大洋洲和亚洲有25亿人生活在危险之中。修订后的《2030年疟疾疫苗技术路线图》认识到间日疟原虫疟疾的严重性，呼吁采取疫苗干预措施，在两年内达到75%的效力，现在与恶性疟原虫同等重要。然而，如果要实现这一目标，迫切需要新的和创新的方法来加速下一代疫苗的研发，同时需要对少数已知的候选抗原进行早期临床评估。在这里，我们以最近在欧洲率先开展的间日疟原虫疫苗研究取得的令人兴奋的突破为基础，包括用于功能测定的新的转基因寄生虫技术，开发和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的目标将围绕疟原虫的生命周期整合雄心勃勃的多学科科学和临床方法，并将利用我们在间日疟原虫免疫生物学方面增加的知识进一步开发具有更高功效的下一代疫苗。我们将通过反向疫苗学使准备用于临床试验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递送多样化。与此同时，将利用创新的临床研究设计和CHMI模型首次对已知主要抗原的疗效进行基准测试，使这些主要候选疫苗为未来的实地试验做好准备。改良的临床前功能分析，使用最先进的转基因寄生虫品系，也将允许破译抗体介导的保护机制。新的功能分析和人体挑战模型的可用性将为临床疫苗界、决策者、资助者和监管机构的知情决策奠定未来框架的基础。

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.