DNA vaccination protects mice against Zika virus-induced damage to the testes.,Nature Communications

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DNA vaccination protects mice against Zika virus-induced damage to the testes.
Nature Communications ( IF 14.7 ) Pub Date : 2017-06-07 , DOI: 10.1038/ncomms15743
Bryan D Griffin _{1,

2} , Kar Muthumani ₃ , Bryce M Warner _{2,

4} , Anna Majer ₅ , Mable Hagan _{1,

2} , Jonathan Audet _{1,

2} , Derek R Stein _{2,

4} , Charlene Ranadheera _{2,

4} , Trina Racine _{1,

6} , Marc-Antoine De La Vega ₆ , Jocelyne Piret ₇ , Stephanie Kucas _{4,

8} , Kaylie N Tran ₁ , Kathy L Frost ₅ , Christine De Graff ₈ , Geoff Soule ₁ , Leanne Scharikow ₄ , Jennifer Scott ₉ , Gordon McTavish ₉ , Valerie Smid ₁₀ , Young K Park ₁₁ , Joel N Maslow ₁₁ , Niranjan Y Sardesai ₁₂ , J Joseph Kim ₁₂ , Xiao-Jian Yao ₂ , Alexander Bello _{1,

2} , Robbin Lindsay _{2,

4} , Guy Boivin ₇ , Stephanie A Booth _{2,

5} , Darwyn Kobasa _{1,

2} , Carissa Embury-Hyatt ₁₀ , David Safronetz _{2,

4} , David B Weiner ₃ , Gary P Kobinger _{6,

13}

Affiliation

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.
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3E 3R2.
Molecular Pathobiology, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, Canada MB R3E 3R2.
Department of Microbiology and Immunology, Faculty of Medicine, Laval University, 1050 avenue de la Médecine, Québec City, Québec, Canada G1V 0A6.
Research Center in Infectious Diseases of the CHU of Québec and Laval University, 2705 boulevard Laurier, Québec City, Quebec, Canada G1V 4G2.
Veterinary Technical Services, Public Health Agency of Canada, National Microbiology Laboratory, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3E 3R2.
Heartland Fertility &Gynecology Clinic, 701-1661 Portage Avenue, Winnipeg, Manitoba, Canada R3J 3T7.
National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3E 3M4.
GeneOne Life Science Inc., 223 Teheran-Ro, Gangnam-Gu, Seoul, Korea.
Inovio Pharmaceuticals Inc., 660 West Germantown Pike, Plymouth Meeting, Pennsylvania 19462, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street Philadelphia, Pennsylvania 19104-4238, USA.

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.

中文翻译：

DNA 疫苗接种可保护小鼠免受寨卡病毒引起的睾丸损伤。

寨卡病毒（ZIKV）是一种新兴病原体，与胎儿严重后遗症有关，诱发胎儿小头畸形和其他神经发育缺陷。 ZIKV 主要通过蚊子传播，但可以在人类精液和精子中持续存在，并且已经有性传播的记录。此外，I型干扰素敲除小鼠接触寨卡病毒后，会导致睾丸、附睾和精子严重受损。候选 ZIKV 疫苗在动物模型中进行的临床前研究中已显示出保护功效，并且多种疫苗已进入临床试验。在这里，我们报告说，注射编码 ZIKV 前膜和包膜 (prME) 的合成 DNA 疫苗可以完全保护小鼠免受 ZIKV 相关的睾丸和精子损伤，并防止现代 ZIKV 毒株攻击后病毒在睾丸中持续存在。这些数据表明 DNA 疫苗接种值得进一步研究，作为减少 ZIKV 在男性生殖道中持续存在的潜在手段。

更新日期：2017-06-12

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