Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

Justin M. Richner; Brett W. Jagger; Chao Shan; Camila R. Fontes; Kimberly A. Dowd; Bin Cao; Sunny Himansu; Elizabeth A. Caine; Bruno T.D. Nunes; Daniele B.A. Medeiros; Antonio E. Muruato; Bryant M. Foreman; Huanle Luo; Tian Wang; Alan D. Barrett; Scott C. Weaver; Pedro F.C. Vasconcelos; Shannan L. Rossi; Giuseppe Ciaramella; Indira U. Mysorekar; Theodore C. Pierson; Pei Yong Shi; Michael S. Diamond

doi:10.1016/j.cell.2017.06.040

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

Justin M. Richner, Brett W. Jagger, Chao Shan, Camila R. Fontes, Kimberly A. Dowd, Bin Cao, Sunny Himansu, Elizabeth A. Caine, Bruno T.D. Nunes, Daniele B.A. Medeiros, Antonio E. Muruato, Bryant M. Foreman, Huanle Luo, Tian Wang, Alan D. Barrett, Scott C. Weaver, Pedro F.C. Vasconcelos, Shannan L. Rossi, Giuseppe Ciaramella, Indira U. MysorekarTheodore C. Pierson, Pei Yong Shi, Michael S. Diamond

Research output: Contribution to journal › Article › peer-review

225 Scopus citations

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.

Original language	English
Pages (from-to)	273-283.e12
Journal	Cell
Volume	170
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2017.06.040
State	Published - Jul 13 2017

Keywords

Vaccine
antibody
fetus
flavivirus
immunity
microcephaly
pregnancy
transmission

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10.1016/j.cell.2017.06.040

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Richner, J. M., Jagger, B. W., Shan, C., Fontes, C. R., Dowd, K. A., Cao, B., Himansu, S., Caine, E. A., Nunes, B. T. D., Medeiros, D. B. A., Muruato, A. E., Foreman, B. M., Luo, H., Wang, T., Barrett, A. D., Weaver, S. C., Vasconcelos, P. F. C., Rossi, S. L., Ciaramella, G., ... Diamond, M. S. (2017). Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease. Cell, 170(2), 273-283.e12. https://doi.org/10.1016/j.cell.2017.06.040

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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 = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = jul,

day = "13",

doi = "10.1016/j.cell.2017.06.040",

language = "English",

volume = "170",

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Richner, JM, Jagger, BW, Shan, C, Fontes, CR, Dowd, KA, Cao, B, Himansu, S, Caine, EA, Nunes, BTD, Medeiros, DBA, Muruato, AE, Foreman, BM, Luo, H, Wang, T, Barrett, AD, Weaver, SC, Vasconcelos, PFC, Rossi, SL, Ciaramella, G, Mysorekar, IU, Pierson, TC, Shi, PY & Diamond, MS 2017, 'Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease', Cell, vol. 170, no. 2, pp. 273-283.e12. https://doi.org/10.1016/j.cell.2017.06.040

TY - JOUR

T1 - Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

AU - Richner, Justin M.

AU - Jagger, Brett W.

AU - Shan, Chao

AU - Fontes, Camila R.

AU - Dowd, Kimberly A.

AU - Cao, Bin

AU - Himansu, Sunny

AU - Caine, Elizabeth A.

AU - Nunes, Bruno T.D.

AU - Medeiros, Daniele B.A.

AU - Muruato, Antonio E.

AU - Foreman, Bryant M.

AU - Luo, Huanle

AU - Wang, Tian

AU - Barrett, Alan D.

AU - Weaver, Scott C.

AU - Vasconcelos, Pedro F.C.

AU - Rossi, Shannan L.

AU - Ciaramella, Giuseppe

AU - Mysorekar, Indira U.

AU - Pierson, Theodore C.

AU - Shi, Pei Yong

AU - Diamond, Michael S.

PY - 2017/7/13

Y1 - 2017/7/13

N2 - 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.

AB - 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.

KW - Vaccine

KW - antibody

KW - fetus

KW - flavivirus

KW - immunity

KW - microcephaly

KW - pregnancy

KW - transmission

UR - http://www.scopus.com/inward/record.url?scp=85023598743&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.06.040

DO - 10.1016/j.cell.2017.06.040

M3 - Article

C2 - 28708997

AN - SCOPUS:85023598743

SN - 0092-8674

VL - 170

SP - 273-283.e12

JO - Cell

JF - Cell

IS - 2

ER -

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

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Keywords

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