Marc-Antoine de La Vega1,2, Jocelyne Piret2, Bryan D Griffin3,4, Chantal Rhéaume2, Marie-Christine Venable2, Julie Carbonneau2, Christian Couture5,6, Raquel das Neves Almeida7, Roland R Tremblay8, Kelly G Magalhães7, Young K Park9, Christine C Roberts9, Joel N Maslow9,10, Niranjan Y Sardesai11, J Joseph Kim11, Kar Muthumani12, David B Weiner12, Gary P Kobinger1,2,4,13, Guy Boivin1,2. 1. Département de Microbiologie-Infectiologie et d'Immunologie, Université Laval, Québec, Canada. 2. Centre de Recherche en Infectiologie du CHU de Québec - Université Laval, Canada. 3. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg. 4. Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. 5. Département d'Anatomo-Pathologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Canada. 6. Département de Biologie Moléculaire, Biochimie Médicale et Pathologie, Université Laval, Québec, Canada. 7. Laboratory of Immunology and Inflammation, University of Brasilia, Brazil. 8. Unité de Recherche en Reproduction, Santé de la Mère et de l'Enfant, Centre de Recherche du CHU de Québec - Université Laval, Canada. 9. GeneOne Life Science Inc., Seoul, Korea. 10. Department of Medicine, Morristown Medical Center, New Jersey. 11. Inovio Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania. 12. The Wistar Institute, Philadelphia, Pennsylvania. 13. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Abstract
Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J. Results: Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males. Conclusions: This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficient mouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.
Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficientmice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J. Results: Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males. Conclusions: This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficientmouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.
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