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

Rafael A Larocca; Erica A Mendes; Peter Abbink; Rebecca L Peterson; Amanda J Martinot; Mark Justin Iampietro; Zi H Kang; Malika Aid; Marinela Kirilova; Catherine Jacob-Dolan; Lisa Tostanoski; Erica N Borducchi; Rafael A De La Barrera; Dan H Barouch

doi:10.1016/j.chom.2019.10.001

Adenovirus Vector-Based Vaccines Confer Maternal-Fetal Protection against Zika Virus Challenge in Pregnant IFN-αβR^-/- Mice

Cell Host Microbe. 2019 Nov 13;26(5):591-600.e4. doi: 10.1016/j.chom.2019.10.001. Epub 2019 Oct 24.

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; University of São Paulo, São Paulo, SP 05508-000, Brazil.
³ Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁴ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: dbarouch@bidmc.harvard.edu.

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-αβR^-/- 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.

Keywords: ZIKV; adenovirus; mouse; pregnancy; vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Adenoviridae / immunology
Animals
Antibodies, Neutralizing / blood*
Antibodies, Neutralizing / immunology
Antibodies, Viral / blood
Antibodies, Viral / immunology
Cell Line
Chlorocebus aethiops
Disease Models, Animal
Female
Immunity, Maternally-Acquired / immunology*
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Pregnancy
Receptor, Interferon alpha-beta / genetics*
Vaccination
Vero Cells
Viral Vaccines / immunology*
Zika Virus / immunology*
Zika Virus Infection / immunology
Zika Virus Infection / prevention & control*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Ifnar1 protein, mouse
Viral Vaccines
Receptor, Interferon alpha-beta