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; Gary P. Kobinger

doi:10.1038/ncomms15743

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 SmidYoung 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

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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.

Original language	English (US)
Article number	15743
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15743
State	Published - Jun 7 2017

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Griffin, B. D., Muthumani, K., Warner, B. M., Majer, A., Hagan, M., Audet, J., Stein, D. R., Ranadheera, C., Racine, T., De La Vega, M. A., Piret, J., Kucas, S., Tran, K. N., Frost, K. L., De Graff, C., Soule, G., Scharikow, L., Scott, J., McTavish, G., ... Kobinger, G. P. (2017). DNA vaccination protects mice against Zika virus-induced damage to the testes. Nature Communications, 8, Article 15743. https://doi.org/10.1038/ncomms15743

Griffin, BD, Muthumani, K, Warner, BM, Majer, A, Hagan, M, Audet, J, Stein, DR, Ranadheera, C, Racine, T, De La Vega, MA, Piret, J, Kucas, S, Tran, KN, Frost, KL, De Graff, C, Soule, G, Scharikow, L, Scott, J, McTavish, G, Smid, V, Park, YK, Maslow, JN, Sardesai, NY, Kim, JJ, Yao, XJ, Bello, A, Lindsay, R, Boivin, G, Booth, SA, Kobasa, D, Embury-Hyatt, C, Safronetz, D, Weiner, DB & Kobinger, GP 2017, 'DNA vaccination protects mice against Zika virus-induced damage to the testes', Nature Communications, vol. 8, 15743. https://doi.org/10.1038/ncomms15743

@article{c681f543218f4cd28926895ced0f7973,

title = "DNA vaccination protects mice against Zika virus-induced damage to the testes",

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.",

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

note = "Funding Information: This study was supported by the Public Health Agency of Canada and D.B.W. was supported in part by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant R01-AI092843); DARPA- PROTECT to D.B.W. and K.M.; BMGF to D.B.W. and K.M. and Inovio Pharmaceuticals to D.B.W. and K.M. Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

month = jun,

day = "7",

doi = "10.1038/ncomms15743",

language = "English (US)",

volume = "8",

journal = "Nature Communications",

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T1 - DNA vaccination protects mice against Zika virus-induced damage to the testes

AU - Griffin, Bryan D.

AU - Muthumani, Kar

AU - Warner, Bryce M.

AU - Majer, Anna

AU - Hagan, Mable

AU - Audet, Jonathan

AU - Stein, Derek R.

AU - Ranadheera, Charlene

AU - Racine, Trina

AU - De La Vega, Marc Antoine

AU - Piret, Jocelyne

AU - Kucas, Stephanie

AU - Tran, Kaylie N.

AU - Frost, Kathy L.

AU - De Graff, Christine

AU - Soule, Geoff

AU - Scharikow, Leanne

AU - Scott, Jennifer

AU - McTavish, Gordon

AU - Smid, Valerie

AU - Park, Young K.

AU - Maslow, Joel N.

AU - Sardesai, Niranjan Y.

AU - Kim, J. Joseph

AU - Yao, Xiao Jian

AU - Bello, Alexander

AU - Lindsay, Robbin

AU - Boivin, Guy

AU - Booth, Stephanie A.

AU - Kobasa, Darwyn

AU - Embury-Hyatt, Carissa

AU - Safronetz, David

AU - Weiner, David B.

AU - Kobinger, Gary P.

N1 - Funding Information: This study was supported by the Public Health Agency of Canada and D.B.W. was supported in part by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant R01-AI092843); DARPA- PROTECT to D.B.W. and K.M.; BMGF to D.B.W. and K.M. and Inovio Pharmaceuticals to D.B.W. and K.M. Publisher Copyright: © The Author(s) 2017.

PY - 2017/6/7

Y1 - 2017/6/7

N2 - 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.

AB - 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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JO - Nature Communications

JF - Nature Communications

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ER -

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

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