Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3E 3R2.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E 0J9.
Nat Commun. 2017 Jun 7;8:15743. doi: 10.1038/ncomms15743.
Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract.
寨卡病毒(ZIKV)是一种新兴病原体,与胎儿的严重后遗症有关,可导致胎儿小头畸形和其他神经发育缺陷。ZIKV 主要通过蚊子传播,但可在人类精液和精子中持续存在,并且已记录到性传播。此外,I 型干扰素敲除小鼠暴露于 ZIKV 会导致睾丸、附睾和精子严重受损。在动物模型中进行的临床前研究表明,候选 ZIKV 疫苗具有保护效力,几种疫苗已进入临床试验。在这里,我们报告称,给予编码 ZIKV 前膜和包膜(prME)的合成 DNA 疫苗可完全保护小鼠免受 ZIKV 相关的睾丸和精子损伤,并防止在接受当代 ZIKV 株攻击后睾丸中的病毒持续存在。这些数据表明,DNA 疫苗值得进一步研究,作为减少男性生殖道中 ZIKV 持续存在的潜在手段。