@article{6ef3fda4b8914ef394d35a70ba8a70d6,
title = "Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease",
abstract = "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.",
keywords = "Vaccine, antibody, fetus, flavivirus, immunity, microcephaly, pregnancy, transmission",
author = "Richner, {Justin M.} and Jagger, {Brett W.} and Chao Shan and Fontes, {Camila R.} and Dowd, {Kimberly A.} and Bin Cao and Sunny Himansu and Caine, {Elizabeth A.} and Nunes, {Bruno T.D.} and Medeiros, {Daniele B.A.} and Muruato, {Antonio E.} and Foreman, {Bryant M.} and Huanle Luo and Tian Wang and Barrett, {Alan D.} and Weaver, {Scott C.} and Vasconcelos, {Pedro F.C.} and Rossi, {Shannan L.} and Giuseppe Ciaramella and Mysorekar, {Indira U.} and Pierson, {Theodore C.} and Shi, {Pei Yong} and Diamond, {Michael S.}",
note = "Funding Information: This work was supported by grants from the NIH-NIAID (R01 AI073755, R01 AI104972, and P01 AI106695 to M.S.D., R24AI120942 to S.C.W., and T32 AI007172 to B.W.J.), the NIH/NICHD (R01 HD091218 to I.U.M. and M.S.D.), the intramural program of NIH-NIAID (T.C.P), a research grant by DARPA (agreement # W911NF-13-1-0417), a Preventing Prematurity Initiative grant from the Burroughs Wellcome Fund (to I.U.M.), a Prematurity Research Initiative Investigator award (21-FY13-28)8 from the March of Dimes (to I.U.M.), and a research grant from Moderna (OTM10991). P.-Y.S. was supported by University of Texas Medical Branch (UTMB) startup award, UTMB Innovation and Commercialization award, University of Texas STARs Award, and a grant from Pan American Health Organization SCON2016-01353. P.F.C.V. was supported by the Ministry of Health of Brazil and by the grants from CNPq (process 303999/2016-0 and 440405/2016-5) and CAPES (Zika fast track project). We thank the Animal Resource Center and Sasha Azar at UTMB for their assistance in maintaining the A129 mouse breeding colony. M.S.D. is a consultant for Inbios, Visterra, and Takeda Pharmaceuticals and on the Scientific Advisory Boards of Moderna and OvaGene. S.C.W. is a consultant for Valera LLC, GeoVax, Inc. and Sanofi-Pasteur. S.H. and G.C. are employees of Valera LLC, a Moderna Venture focusing on the development of therapeutic approaches for Infectious Diseases, including ZIKV mRNA vaccines. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jul,
day = "13",
doi = "10.1016/j.cell.2017.06.040",
language = "English",
volume = "170",
pages = "273--283.e12",
journal = "Cell",
issn = "0092-8674",
number = "2",
}