病毒学
中和抗体
抗体
效价
生物
免疫系统
寨卡病毒
免疫
病毒载量
病毒载体
免疫学
病毒
医学
重组DNA
生物化学
基因
作者
Qiang Guo,Jasper Fuk‐Woo Chan,Vincent Kwok-Man Poon,Shipo Wu,Chris Chan,Lihua Hou,Cyril Chik-Yan Yip,Changpeng Ren,Jian‐Piao Cai,Mengsu Zhao,Anna Jinxia Zhang,Xiaohong Song,Kwok-Hung Chan,Busen Wang,Kin‐Hang Kok,Yanbo Wen,Kwok‐Yung Yuen,Wei Chen
标识
DOI:10.1093/infdis/jiy187
摘要
Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain.We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains.Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-α/β receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice.Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.
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