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

Bryan D. Griffin, Kar Muthumani, Bryce M. Warner, Anna Majer, Mable Hagan, Jonathan Audet, Derek R. Stein, Charlene Ranadheera, Trina Racine, Marc-Antoine De La Vega, 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 and Gary P. Kobinger ()
Additional contact information
Bryan D. Griffin: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Kar Muthumani: The Wistar Institute
Bryce M. Warner: University of Manitoba
Anna Majer: Molecular Pathobiology, National Microbiology Laboratory, Public Health Agency of Canada
Mable Hagan: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Jonathan Audet: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Derek R. Stein: University of Manitoba
Charlene Ranadheera: University of Manitoba
Trina Racine: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Marc-Antoine De La Vega: Faculty of Medicine, Laval University
Jocelyne Piret: Research Center in Infectious Diseases of the CHU of Québec and Laval University
Stephanie Kucas: Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada
Kaylie N. Tran: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Kathy L. Frost: Molecular Pathobiology, National Microbiology Laboratory, Public Health Agency of Canada
Christine De Graff: Veterinary Technical Services, Public Health Agency of Canada, National Microbiology Laboratory
Geoff Soule: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Leanne Scharikow: Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada
Jennifer Scott: Heartland Fertility & Gynecology Clinic
Gordon McTavish: Heartland Fertility & Gynecology Clinic
Valerie Smid: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency
Young K. Park: GeneOne Life Science Inc.
Joel N. Maslow: GeneOne Life Science Inc.
Niranjan Y. Sardesai: Inovio Pharmaceuticals Inc.
J. Joseph Kim: Inovio Pharmaceuticals Inc.
Xiao-jian Yao: University of Manitoba
Alexander Bello: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Robbin Lindsay: University of Manitoba
Guy Boivin: Research Center in Infectious Diseases of the CHU of Québec and Laval University
Stephanie A. Booth: University of Manitoba
Darwyn Kobasa: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada
Carissa Embury-Hyatt: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency
David Safronetz: University of Manitoba
David B. Weiner: The Wistar Institute
Gary P. Kobinger: Faculty of Medicine, Laval University

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15743

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