单价型嵌合登革热 2 型/寨卡病毒候选疫苗可保护小鼠和非人灵长类动物免受寨卡病毒感染。

Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus.

机构信息

Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA.

Takeda Vaccines Inc., Cambridge, MA, USA.

出版信息

Nat Commun. 2021 Dec 16;12(1):7320. doi: 10.1038/s41467-021-27578-w.

DOI:10.1038/s41467-021-27578-w

PMID:34916486

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8677809/

Abstract

The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.

摘要

自 2015-2016 年广泛流行以来，开发安全有效的寨卡病毒（ZIKV）疫苗已成为全球卫生重点。基于使用特征良好和临床证实的登革热病毒血清型 2（DENV-2）PDK-53 疫苗骨架用于开发活减毒嵌合黄病毒疫苗的先前经验，我们开发了针对在 Vero 细胞中生长和遗传稳定性进行了优化的嵌合 DENV-2/ZIKV 疫苗候选物。这些候选疫苗保留了 PDK-53 疫苗病毒的所有先前特征的衰减表型，包括对 1 日龄 CD-1 小鼠的神经毒力衰减，在干扰素受体缺陷型小鼠中无毒力，以及在主要蚊媒中无传播能力。单次 DENV-2/ZIKV 剂量可提供针对 ZIKV 挑战的保护，减少小鼠和恒河猴中的 ZIKV 感染。总体而言，这些数据表明，这些 ZIKV 活减毒疫苗候选物在多种动物模型中是安全的、具有免疫原性的且能有效预防 ZIKV 感染，值得进一步开发。