Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine

Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A Weaver

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a T-cell response. In a highly lethal challenge in an interferon α/β receptor knockout mice, 80% of Ad5 vaccinated animals and 33% of Ad4 vaccinated animals survived a lethal ZIKV challenge, whereas no animals in the sham vaccinated group survived. In an infection model utilizing immunocompetent C57BL/6 mice that were immunized and then treated with a blocking anti-IFNAR-1 antibody immediately before ZIKV challenge, 100% of Ad4-prM-E and Ad5-prM-E vaccinated mice survived. This indicates that Ad4-prM-E vaccination is protective without the development of detectable anti-ZIKV antibodies. The protection seen in these highly lethal mouse models demonstrate the efficacy of Ad vectored vaccines for use against ZIKV.

Original languageEnglish (US)
Article number18017
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Adenoviridae
Vaccines
T-Lymphocytes
Vaccination
Antibodies
Adenovirus Vaccines
Interferon Receptors
Human Adenoviruses
Guillain-Barre Syndrome
Zika Virus
Humoral Immunity
Infection
Inbred C57BL Mouse
Knockout Mice
Cellular Immunity
Fetus
Public Health
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine. / Bullard, Brianna L.; Corder, Brigette N.; Gorman, Matthew J.; Diamond, Michael S.; Weaver, Eric A.

In: Scientific reports, Vol. 8, No. 1, 18017, 01.12.2018.

Research output: Contribution to journalArticle

Bullard, Brianna L. ; Corder, Brigette N. ; Gorman, Matthew J. ; Diamond, Michael S. ; Weaver, Eric A. / Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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