A Randomized Phase I Clinical Trial of HydroVax-CHIKV, a Novel Inactivated Chikungunya Virus Vaccine

基孔肯雅病毒(CHIKV)是一种甲型病毒，由于其能够引起巨大的 在易感人群中传播流行病，并通过国际旅行者传播到流行国家以外的国家。 在法国留尼汪岛约75万人口中，有26.6万人感染 2006年暴发期间发生了200多起与CHIKV有关的死亡事件。同样，估计有140万人 在2006年至2007年期间和最近的印度，人们感染了CHIKV病毒 在加勒比海和美洲已有170多万人感染了CHIKV。目前， 目前还没有针对CHIKV的商业疫苗。一种适用于CHIKV灭活疫苗的研制 为普通人群以及包括婴儿和老年人在内的弱势群体接种疫苗 一个重要的未得到满足的临床需求。为了解决这一关键的未得到满足的需求，我们发现了一种安全和 免疫原性过氧化氢灭活基孔肯雅病毒疫苗。重要的是，这一先进的 疫苗是安全的，对感染和CHIKV相关病理提供完全保护 老鼠模型。在这里，我们提出了一项双盲、随机、安慰剂对照的第一阶段剂量递增试验 初步评价水痘疫苗的安全性和免疫原性。我们的目标是最终提供 疫苗覆盖到弱势人群和这项研究的成功完成将是一个关键 在临床上相关的基孔肯雅病毒疫苗的进展方面具有里程碑意义，并提供了一种 需要采取措施保护社会上最易受影响的成员，包括婴儿、老年人和有 可能会损害免疫功能。

Chikungunya virus (CHIKV) is an alphavirus that has gained significant attention due to its ability to cause large epidemics among susceptible populations and to be spread beyond endemic countries by international travelers. Among a population of approximately 750,000 on the French island of La Reunion, 266,000 people were infected and over 200 CHIKV-related fatalities occurred during the 2006 outbreak. Likewise, an estimated 1.4 million people were infected with CHIKV in India during outbreaks that occurred from 2006 to 2007 and recently there have been more than 1.7 million people infected with CHIKV in the Caribbean and the Americas. At present, there is no commercial vaccine available for CHIKV. The development of an inactivated CHIKV vaccine suitable for immunizing the general population as well as vulnerable groups including infants and the elderly represents an important unmet clinical need. To address this critical unmet need, we have discovered a safe and immunogenic peroxide-inactivated chikungunya virus vaccine, HydroVax-CHIKV. Importantly, this advanced vaccine is safe and provides complete protection against infection and CHIKV-associated pathology in a robust mouse model. Here, we propose a double-blind, randomized, placebo-controlled Phase 1 dose escalation trial to evaluate the preliminary safety and immunogenicity of HydroVax-CHIKV. Our goal is to eventually provide vaccine coverage to vulnerable populations and the successful completion of this study will represent a key milestone in the advancement of a clinically relevant vaccine against chikungunya virus and provide a much- needed approach to protect the most susceptible members of society including infants, elderly, and those with potentially compromised immune functions.