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

被引:80
作者
Griffin, Bryan D. [1 ,2 ]
Muthumani, Kar [3 ]
Warner, Bryce M. [2 ,4 ]
Majer, Anna [5 ]
Hagan, Mable [1 ,2 ]
Audet, Jonathan [1 ,2 ]
Stein, Derek R. [2 ,4 ]
Ranadheera, Charlene [2 ,4 ]
Racine, Trina [1 ,6 ]
De la Vega, Marc-Antoine [6 ]
Piret, Jocelyne [7 ,8 ]
Kucas, Stephanie [4 ,9 ]
Tran, Kaylie N.
Frost, Kathy L. [1 ,5 ]
De Graff, Christine [9 ]
Soule, Geoff [1 ]
Scharikow, Leanne [4 ]
Scott, Jennifer [10 ]
McTavish, Gordon [10 ]
Smid, Valerie [11 ]
Park, Young K. [12 ]
Maslow, Joel N. [12 ]
Sardesai, Niranjan Y. [13 ]
Kim, J. Joseph [13 ]
Yao, Xiao-jian [2 ]
Bello, Alexander [1 ,2 ]
Lindsay, Robbin [2 ,4 ]
Boivin, Guy [7 ,8 ]
Booth, Stephanie A. [2 ,5 ]
Kobasa, Darwyn [1 ,2 ]
Embury-Hyatt, Carissa [11 ]
Safronetz, David [2 ,4 ]
Weiner, David B. [3 ]
Kobinger, Gary P. [6 ,14 ]
机构
[1] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada
[2] Univ Manitoba, Dept Med Microbiol & Infect Dis, 745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada
[3] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA
[4] Publ Hlth Agcy Canada, Natl Microbiol Lab, Zoonot Dis & Special Pathogens, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada
[5] Publ Hlth Agcy Canada, Natl Microbiol Lab, Mol Pathobiol, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada
[6] Laval Univ, Fac Med, Dept Microbiol & Immunol, 1050 Ave Med, Quebec City, PQ G1V 0A6, Canada
[7] CHU Quebec, Res Ctr Infect Dis, 2705 Blvd Laurier, Quebec City, PQ G1V 4G2, Canada
[8] Laval Univ, 2705 Blvd Laurier, Quebec City, PQ G1V 4G2, Canada
[9] Publ Hlth Agcy Canada, Natl Microbiol Lab, Vet Tech Serv, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada
[10] Heartland Fertil & Gynecol Clin, 701-1661 Portage Ave, Winnipeg, MB R3J 3T7, Canada
[11] Canadian Food Inspect Agcy, Natl Ctr Foreign Anim Dis, 1015 Arlington St, Winnipeg, MB R3E 3M4, Canada
[12] GeneOne Life Sci Inc, 223 Teheran Ro, Seoul, South Korea
[13] Inovio Pharmaceut Inc, 660 West Germantown Pike, Plymouth Meeting, PA 19462 USA
[14] Univ Penn, Sch Med, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
SEXUAL TRANSMISSION; INFECTION; INHIBITORS; SEMEN;
D O I
10.1038/ncomms15743
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:8
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