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

• DOI: 10.1038/ncomms15743
• Publication Date: 2017-06-07T10:04:20Z
• Authors: Bryan D. Griffin; Kar Muthumani; Bryce M. Warner; Anna Majer; Mable Hagan; Jonathan Audet; Derek R. Stein; Charlene Ranadheera; Trina Racine; Marc-Antoine De L...; Jocelyne Piret; Stephanie Kucas; Kaylie N. Tran; Kathy L. Frost; Christine De Graff; Geoff Soule; Leanne Scharikow; Jennifer Scott; Gordon McTavish; Valerie Smid; Young K. Park; Joel N. Maslow; Niranjan Y. Sardesai; J. Joseph Kim; Xiao-jian Yao; Alexander Bello; Robbin Lindsay; Guy Boivin; Stephanie A. Booth; Darwyn Kobasa; Carissa Embury-Hyatt; David Safronetz; David B. Weiner; Gary P. Kobinger
• Keywords: Male; Mice, Knockout; 0301 basic medicine; 0303 health sciences; Zika Virus Infection; Science; Q; Viral Vaccines; Receptor, Interferon alpha-beta; Zika Virus; Spermatozoa; Article; 3. Good health; 03 medical and health sciences; Viral Envelope Proteins; Testis; Vaccines, DNA; Animals

AbstractZika 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.