Journal Article

DNA vaccination protects mice against Zika virus-induced damage to the testes

De Graff, Christine, Booth, Stephanie A., Piret, Jocelyne, Soule, Geoff, Ranadheera, Charlene, Racine, Trina, Lindsay, Robbin, Hagan, Mable, Warner, Bryce M., McTavish, Gordon, Weiner, David B., Sardesai, Niranjan Y., Boivin, Guy, De La Vega, Marc-Antoine, Kobasa, Darwyn, Muthumani, Kar, Kim, J. Joseph, Majer, Anna, Scharikow, Leanne, Griffin, Bryan D., Smid, Valerie, Maslow, Joel N., Yao, Xiao-jian, Embury-Hyatt, Carissa, Kucas, Stephanie, Frost, Kathy L., Bello, Alexander, Kobinger, Gary P., Tran, Kaylie N., Stein, Derek R., Safronetz, David, Park, Young K., Scott, Jennifer, Audet, Jonathan

2017

Overview

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. Zika virus (ZIKV) can persist in human semen and sperm, which can result in sexual transmission. Here, Griffin et al . show that a DNA vaccine, expressing ZIKV pre-membrane and envelope proteins, protects mice from infection-associated damage to testes and sperm, and prevents viral persistence in testes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/326/590/1991 / 631/326/596/2555 / 64 / Animal models / Animals / Deoxyribonucleic acid / DNA / Drug dosages / Fetuses / Humanities and Social Sciences / Immunization / Infections / Infectious diseases / Laboratories / Male / Mice, Knockout / Microcephaly / multidisciplinary / Pathogens / Public health / Receptor, Interferon alpha-beta - genetics / Science / Science (multidisciplinary) / Sperm / Spermatozoa - pathology / Spermatozoa - virology / Testes / Testis - pathology / Testis - virology / Vaccines / Vaccines, DNA - pharmacology / Variance analysis / Vector-borne diseases / Viral Envelope Proteins - genetics / Viral Vaccines - pharmacology / Zika virus / Zika Virus - genetics / Zika Virus - pathogenicity / Zika Virus Infection - physiopathology / Zika Virus Infection - prevention & control