Dataset Information

Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-??R-/- Mice.

ABSTRACT: Maternal infection with Zika virus (ZIKV) can lead to microcephaly and other congenital abnormalities of the fetus. Although ZIKV vaccines that prevent or reduce viremia in non-pregnant mice have been described, a maternal vaccine that provides complete fetal protection would be desirable. Here, we show that adenovirus (Ad) vector-based ZIKV vaccines induce potent neutralizing antibodies that confer robust maternal and fetal protection against ZIKV challenge in pregnant, highly susceptible IFN-??R-/- mice. Moreover, passive transfer of maternal antibodies from vaccinated dams protected pups against post-natal ZIKV challenge. These data suggest that Ad-based ZIKV vaccines may be able to provide protection in pregnant females against fetal ZIKV transmission in utero as well as in infants against ZIKV infection after birth.

SUBMITTER: Larocca RA

PROVIDER: S-EPMC6863051 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-αβR<sup>-/-</sup> Mice.

Larocca Rafael A RA Mendes Erica A EA Abbink Peter P Peterson Rebecca L RL Martinot Amanda J AJ Iampietro Mark Justin MJ Kang Zi H ZH Aid Malika M Kirilova Marinela M Jacob-Dolan Catherine C Tostanoski Lisa L Borducchi Erica N EN De La Barrera Rafael A RA Barouch Dan H DH

Cell host & microbe 20191024 5

Maternal infection with Zika virus (ZIKV) can lead to microcephaly and other congenital abnormalities of the fetus. Although ZIKV vaccines that prevent or reduce viremia in non-pregnant mice have been described, a maternal vaccine that provides complete fetal protection would be desirable. Here, we show that adenovirus (Ad) vector-based ZIKV vaccines induce potent neutralizing antibodies that confer robust maternal and fetal protection against ZIKV challenge in pregnant, highly susceptible IFN-α ...[more]

PMID: 31668877

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Project description:BackgroundZika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Methodology/principal findingsUsing our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.Conclusions/significanceAn effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.

Dataset Information

Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-??R-/- Mice.

Publications

Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-αβR<sup>-/-</sup> Mice.

Similar Datasets

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