Vaccine mediated protection against Zika virus-induced congenital disease

Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD. USA Washington University School of Medicine. Department of Obstetrics and Gynecology. St. Louis, MO, USA. Moderna Venture. Valera LLC. Technology Square. Cambridge, MA, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD, USA. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Vaccine Development. Galveston, TX, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Par? State University. Department of Pathology. Bel?m, PA, Brazil. University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA. Moderna Venture. Valera LLC. Technology Square. Cambridge, MA, USA. Washington University School of Medicine. Department of Obstetrics and Gynecology. St. Louis, MO, USA / Washington University School of Medicine. Department of Pathology and Immunology. St. Louis, MO, USA. National Institutes of Health. Laboratory of Viral Diseases. Viral Pathogenesis Section. Bethesda, MD, USA. University of Texas Medical Branch. Department of Biochemistry & Molecular Biology. Galveston, TX, USA / University of Texas Medical Branch. Institute for Translational Science. Galveston, TX, USA / University of Texas Medical Branch. Institute for Human infections and Immunity. Galveston, TX, USA / University of Texas Medical Branch. Department of Pharmacology & Toxicology. Galveston, TX, USA / University of Texas Medical Branch. Sealy Center for Structural Biology & Molecular Biophysics. Galveston, TX, USA. Washington University School of Medicine. Department of Medicine. St. Louis, MO, USA / Washington University School of Medicine. Department of Pathology and Immunology. St. Louis, MO, USA / Washington University School of Medicine. Department of Molecular Microbiology. St. Louis, MO, USA / Washington University School of Medicine. The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs. St. Louis, MO, USA. The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.