Abstract
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.
Highlights
Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects
We report that delivery of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) prior to a high-dose challenge with a contemporary strain of ZIKV completely protects mice against ZIKV-associated damage to the testes and sperm and prevents persistence of ZIKV in the testes and epididymis
To investigate vaccinemediated protection against testicular damages, prime-boost immunizations of Ifnar[1] À / À mice consisting of intra muscular (i.m.) injection followed by electroporation-mediated delivery of a prME DNA vaccine at 2-week intervals were performed prior to a ZIKV challenge with 1 Â 106 p.f.u. at 10 weeks of age
Summary
Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. 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. We report that delivery of a synthetic DNA vaccine encoding ZIKV prME prior to a high-dose challenge with a contemporary strain of ZIKV completely protects mice against ZIKV-associated damage to the testes and sperm and prevents persistence of ZIKV in the testes and epididymis These data suggest that DNA vaccination and investigational therapeutics warrant further examination as a potential means to reduce ZIKV persistence in the male reproductive tract
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