一种针对寨卡病毒的单剂量减毒活嵌合候选疫苗。

A single-dose live attenuated chimeric vaccine candidate against Zika virus.

作者信息

Chin Wei-Xin, Lee Regina Ching Hua, Kaur Parveen, Lew Tian Sheng, Yogarajah Thinesshwary, Kong Hao Yuin, Teo Zi-Yun, Salim Cyrill Kafi, Zhang Rong-Rong, Li Xiao-Feng, Alonso Sylvie, Qin Cheng-Feng, Chu Justin Jang Hann

机构信息

Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, MD4 Level 5, 5 Science Drive 2, Singapore, 117597, Singapore.

NUSMed Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599, Singapore.

出版信息

NPJ Vaccines. 2021 Jan 29;6(1):20. doi: 10.1038/s41541-021-00282-y.

The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.

由蚊子传播的寨卡病毒是黄病毒属的一种新出现的病原体，目前尚无获批的抗病毒药物或疫苗。我们以临床验证的PDK - 53登革病毒疫苗株为基础，构建了一种嵌合登革热/寨卡病毒VacDZ，作为一种针对寨卡病毒的减毒活疫苗候选物。VacDZ表现出减毒的关键特征：小噬斑表型、温度敏感性、对乳鼠神经毒力的减弱以及在干扰素缺陷的成年AG129小鼠中致病性的减弱。VacDZ可以作为传统的活病毒疫苗给药，也可以作为DNA启动疫苗给药，后者在给药后在体内产生活的VacDZ。两种疫苗剂型均可在AG129小鼠中诱导针对寨卡病毒的保护性免疫反应，包括中和抗体和强烈的Th1反应。本研究表明，VacDZ是一种针对寨卡病毒的安全有效的疫苗候选物。