A simple, multivalent vaccine to prevent Zika and Chikungunya: progression and readiness to phase II trial

该项目的目的是推进新型二价疫苗的临床开发，该疫苗明智地诱导同时针对寨卡病毒和基孔肯雅病毒（ZIKV 和 CHIKV）提供保护。这两种疾病与登革热由同一种蚊子传播，因此在相同地理区域和相同人群中造成严重的疾病负担，特别是在低收入和中等收入国家。目前还没有疫苗可以预防寨卡病毒或基孔肯雅热感染，虽然任何一种疫苗都特别有助于减轻这些弱势群体的疾病负担，但与单一疫苗接种活动相比，二价疫苗将通过以更低的成本简化疫苗接种活动，进一步支持全球健康。 ZIKV 感染是世界范围内的一个主要问题，因为它会引起神经系统疾病，例如吉兰-巴利综合征，并使新生儿小头畸形的发病率增加 20 倍。 CHIKV 感染会导致大约四分之三的感染者出现类似流感的症状，并可能导致所有年龄段的患者出现疼痛和衰弱的长期关节炎。持续性关节炎可能持续数年，导致残疾和无法工作。对于 ZIKV 和 CHIKV 感染的长期后遗症和缺乏针对性治疗，在卫生系统薄弱且已被登革热等其他虫媒病毒疾病或 SARS-CoV-2 等无关疫情爆发的地区不堪重负，导致贫困和家庭和政府的高昂费用。贫困和移民等社会经济因素以及气候变化增加了蚊子生存和传播病毒的地理区域。一个重大突破和理想的预防解决方案是提供一种二价疫苗来同时对抗寨卡和基孔肯雅热。该提案旨在利用在墨西哥完成的 Ib 期试验中收集的结果和样本，这两种疾病在墨西哥都很流行。这个为期 12 个月的项目将使合作伙伴能够推进技术工具和合作，为 IIb 期临床试验做好准备。

The aim of this project is to progress the clinical development of a new bivalent vaccine that judiciously induces simultaneous protection against Zika and chikungunya viruses (ZIKV and CHIKV). These two diseases are transmitted by the same mosquito specie as dengue, therefore causing a severe disease burden in the same geographical regions and in the same populations, particularly in low-and-middle-income countries. There is currently no vaccine to prevent Zika or chikungunya infections, and while any one vaccine would be particularly useful to reduce the disease burden in these vulnerable populations, a bivalent vaccine would further support global health by simplifying vaccination campaigns at lower costs when compared to single vaccine campaigns. Infection by ZIKV is a major concern worldwide due to causing neurologic conditions, such as Guillain-Barré syndrome and a 20-fold increase in the incidence of neonatal microcephaly. Infection by CHIKV results in a flu-like symptomatic disease in approximately three quarters of infected people, and may lead to painful and debilitating long-term arthritis in patients of all ages. Persistent arthritis may last for years causing disability and inability to work. Long-term sequelae and lack of specific treatment for ZIKV and CHIKV infections contribute to poverty and high costs for families and governments in areas where the health system is weak and already overwhelmed by other arbovirus diseases such as dengue or by unrelated outbreaks such as SARS-CoV-2\. Socioeconomical factors such as poverty and migration, together with climate change, increase the geographical regions where the mosquitoes live and transmit the viruses. A major breakthrough and an ideal preventive solution would be to provide a bivalent vaccine to simultaneously fight Zika and chikungunya. This proposal aims to leverage the findings and samples collected during a Phase Ib trial that has been completed in Mexico, where both diseases are prevalent. This 12-month project will enable the partners to advance the technical tools and collaborations ready for a phase IIb clinical trial.