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Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation

机译:寨卡疫苗开发的现状:寨卡疫苗进入临床评估

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摘要

Zika virus (ZIKV), a mosquito-borne flavivirus, was first identified in the 1940s in Uganda in Africa and emerged in the Americas in Brazil in May 2015. In the 30 months since ZIKV emerged as a major public health problem, spectacular progress has been made with vaccine development cumulating with the publication of three reports of phase 1 clinical trials in the 4th quarter of 2017. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralizing antibodies, although these varied by vaccine candidate and dosing regimen. These results suggest that a Zika vaccine can be developed and that phase 2 clinical trials are warranted. However, it is difficult to compare the results from the different phase 1 studies or with neutralizing antibodies induced by licensed flavivirus vaccines (Japanese encephalitis, tick-borne encephalitis, and yellow fever) as neutralizing antibody assays vary and, unfortunately, there are no standards for Zika virus neutralizing antibodies. In addition to clinical studies, substantial progress continues to be made in nonclinical development, particularly in terms of the ability of candidate vaccines to protect reproductive tissues, and the potential use of monoclonal antibodies for passive prophylaxis.
机译:寨卡病毒(ZIKV)是一种由蚊子传播的黄病毒,最早于1940年代在非洲乌干达发现,并于2015年5月在巴西美洲出现。在ZIKV成为主要的公共卫生问题后的30个月中,取得了长足发展疫苗开发已经完成,并于2017年第四季度发表了三份第一期临床试验报告。涉及候选DNA和纯化的灭活病毒疫苗的临床试验表明,在少数志愿者中,所有药物都是安全且耐受性良好的,诱导中和抗体,尽管这些抗体因候选疫苗和给药方案而异。这些结果表明可以开发Zika疫苗,并且有必要进行2期临床试验。但是,由于中和抗体的测定方法各不相同,因此很难比较不同的1期研究结果或由许可的黄病毒疫苗(日本脑炎,tick传脑炎和黄热病)诱导的中和抗体的结果,而且遗憾的是,目前尚无标准Zika病毒中和抗体。除临床研究外,非临床研究仍继续取得实质性进展,特别是在候选疫苗保护生殖组织的能力以及单克隆抗体用于被动预防方面的潜在应用方面。

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