Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

• Published in: Cell 2017-07, Vol.170 (2), p.273-283.e12
• Main Authors: Richner, Justin M., Jagger, Brett W., Shan, Chao, Fontes, Camila R., Dowd, Kimberly A., Cao, Bin, Himansu, Sunny, Caine, Elizabeth A., Nunes, Bruno T.D., Medeiros, Daniele B.A., Muruato, Antonio E., Foreman, Bryant M., Luo, Huanle, Wang, Tian, Barrett, Alan D., Weaver, Scott C., Vasconcelos, Pedro F.C., Rossi, Shannan L., Ciaramella, Giuseppe, Mysorekar, Indira U., Pierson, Theodore C., Shi, Pei-Yong, Diamond, Michael S.
• Format: Article
• Language: English
• Subjects: Aedes - virology; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; antibody; Blood Cells - virology; Embryo, Mammalian - virology; Female; fetus; Fetus - virology; flavivirus; Humans; immunity; Lipids - administration & dosage; Male; Mice; Mice, Inbred C57BL; microcephaly; Mutation; pregnancy; RNA, Messenger - genetics; RNA, Messenger - immunology; Specific Pathogen-Free Organisms; transmission; Vaccine; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; Zika Virus - physiology; Zika Virus Infection - immunology; Zika Virus Infection - prevention & control; Zika Virus Infection - virology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2017.06.040

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. [Display omitted] •Modified mRNA and live attenuated ZIKV vaccines protect during pregnancy in mice•High titers of neutralizing antibodies are achieved by both vaccine platforms•Vaccines block ZIKV transmission to the fetus in most animals•Damage to the placenta and fetus is prevented Immunization of pregnant animals with Zika virus vaccines protects the fetuses against vertical transmission of the virus, placental disease, and fetal demise.