Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus during Pregnancy in Mice

Brett W. Jagger; Kimberly A. Dowd; Rita E. Chen; Pritesh Desai; Bryant Foreman; Katherine E. Burgomaster; Sunny Himansu; Wing Pui Kong; Barney S. Graham; Theodore C. Pierson; Michael S. Diamond

doi:10.1093/infdis/jiz338

Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus during Pregnancy in Mice

Brett W. Jagger, Kimberly A. Dowd, Rita E. Chen, Pritesh Desai, Bryant Foreman, Katherine E. Burgomaster, Sunny Himansu, Wing Pui Kong, Barney S. Graham, Theodore C. Pierson, Michael S. Diamond

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

25 Scopus citations

Abstract

Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

Original language	English
Pages (from-to)	1577-1588
Number of pages	12
Journal	Journal of Infectious Diseases
Volume	220
Issue number	10
DOIs	https://doi.org/10.1093/infdis/jiz338
State	Published - Oct 8 2019

Keywords

Zika
congenital Zika syndrome
neutralizing antibody
pregnancy
vaccine
vaccine

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@article{104ed1d3372949eca9e3cb528ec9e9c8,

title = "Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus during Pregnancy in Mice",

abstract = "Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.",

keywords = "Zika, congenital Zika syndrome, neutralizing antibody, pregnancy, vaccine, vaccine",

author = "Jagger, {Brett W.} and Dowd, {Kimberly A.} and Chen, {Rita E.} and Pritesh Desai and Bryant Foreman and Burgomaster, {Katherine E.} and Sunny Himansu and Kong, {Wing Pui} and Graham, {Barney S.} and Pierson, {Theodore C.} and Diamond, {Michael S.}",

note = "Funding Information: Financial support. This work was supported by the National Institutes of Health (NIH; grants R01 AI073755 and R01 HD091218 to M. S. D. and grant T32 AI007172 to B. W. J.), the National Institute of Allergy and Infectious Diseases Intramural Research Program (grants to T. C. P. and B. S. G.), and Moderna. Funding Information: We thank Lingshu Wang and Sung- Youl Ko, for assistance with vaccinations; and Kaitlyn Morabito, for project management. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",

year = "2019",

month = oct,

day = "8",

doi = "10.1093/infdis/jiz338",

language = "English",

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pages = "1577--1588",

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T1 - Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus during Pregnancy in Mice

AU - Jagger, Brett W.

AU - Dowd, Kimberly A.

AU - Chen, Rita E.

AU - Desai, Pritesh

AU - Foreman, Bryant

AU - Burgomaster, Katherine E.

AU - Himansu, Sunny

AU - Kong, Wing Pui

AU - Graham, Barney S.

AU - Pierson, Theodore C.

AU - Diamond, Michael S.

N1 - Funding Information: Financial support. This work was supported by the National Institutes of Health (NIH; grants R01 AI073755 and R01 HD091218 to M. S. D. and grant T32 AI007172 to B. W. J.), the National Institute of Allergy and Infectious Diseases Intramural Research Program (grants to T. C. P. and B. S. G.), and Moderna. Funding Information: We thank Lingshu Wang and Sung- Youl Ko, for assistance with vaccinations; and Kaitlyn Morabito, for project management. Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2019/10/8

Y1 - 2019/10/8

N2 - Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

AB - Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015-2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling-deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

KW - Zika

KW - congenital Zika syndrome

KW - neutralizing antibody

KW - pregnancy

KW - vaccine

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AN - SCOPUS:85073081024

SN - 0022-1899

VL - 220

SP - 1577

EP - 1588

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 10

ER -

Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus during Pregnancy in Mice

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