Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, 75005 Paris, France; Ecole Doctorale Frontières du Vivant (FdV), 26 Rue de l'Étoile, 75017 Paris, France.
Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France.
Mol Ther. 2020 Aug 5;28(8):1772-1782. doi: 10.1016/j.ymthe.2020.05.016. Epub 2020 May 20.
Zika virus, a member of the Flaviviridae family, is primarily transmitted by infected Aedes species mosquitoes. In 2016, Zika infection emerged as a global health emergency for its explosive spread and the remarkable neurological defects in the developing fetus. Development of a safe and effective Zika vaccine remains a high priority owing to the risk of re-emergence and limited understanding of Zika virus epidemiology. We engineered a non-integrating lentiviralvector(NILV)-based Zika vaccine encoding the consensus pre-membrane and envelope glycoprotein of circulating Zika virus strains. We further evaluated the immunogenicity and protective efficacy of this vaccine in both immunocompromised and immunocompetent mouse models. A single immunization in both mouse models elicited a robust neutralizing antibody titer and afforded full protection against Zika challenge as early as 7 days post-immunization. This NILV-based vaccine also induced a long-lasting immunity when immunized mice were challenged 6 months after immunization. Altogether, our NILV Zika vaccine provides a rapid yet durable protection through a single dose of immunization without extra adjuvant formulation. Our data suggest a promising Zika vaccine candidate for an emergency situation, and demonstrate the capacity of lentiviral vector as an efficient vaccine delivery platform.
寨卡病毒属于黄病毒科,主要通过受感染的伊蚊属蚊子传播。2016 年,寨卡病毒的爆发式传播及其对发育中胎儿的显著神经缺陷,使其成为全球卫生紧急事件。由于存在再次出现的风险,而且对寨卡病毒的流行病学了解有限,因此开发安全有效的寨卡病毒疫苗仍然是当务之急。我们构建了一种基于非整合慢病毒载体(NILV)的寨卡病毒疫苗,该疫苗编码循环的寨卡病毒株的包膜糖蛋白前膜和包膜糖蛋白。我们进一步评估了这种疫苗在免疫功能低下和免疫功能正常的小鼠模型中的免疫原性和保护效力。在两种小鼠模型中,单次免疫即可产生强大的中和抗体滴度,并在免疫后 7 天内提供针对寨卡病毒挑战的完全保护。在免疫后 6 个月再次免疫接种时,这种基于 NILV 的疫苗也诱导了持久的免疫力。总之,我们的 NILV 寨卡病毒疫苗通过单次免疫接种即可快速且持久地提供保护,而无需额外的佐剂配方。我们的数据为紧急情况下提供了一种有前途的寨卡病毒疫苗候选物,并证明了慢病毒载体作为一种有效的疫苗传递平台的能力。