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Cell Rep. 2019 Sep 3;28(10):2634-2646.e4. doi: 10.1016/j.celrep.2019.08.005.

A Gorilla Adenovirus-Based Vaccine against Zika Virus Induces Durable Immunity and Confers Protection in Pregnancy.

Author information

1
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Precigen, 20358 Seneca Meadows Parkway, Germantown, MD 20876, USA.
5
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.

Abstract

The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD8+ T cell independent, and for GAd-Eecto requires the complement component C1q. Immunization of GAd-Zvp induces antibodies against a key neutralizing epitope on domain III of E protein and confers durable protection as evidenced by memory B and long-lived plasma cell responses and challenge studies 9 months later. In two models of ZIKV infection during pregnancy, GAd-Zvp prevents maternal-to-fetal transmission. The gorilla adenovirus-based vaccine platform encoding full-length prM and E genes is a promising candidate for preventing congenital ZIKV syndrome and possibly infection by other flaviviruses.

KEYWORDS:

Zika virus; adaptive immunity; flavivirus; pathogenesis; pregnancy; vaccine

PMID:
31484074
DOI:
10.1016/j.celrep.2019.08.005
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