Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus.

Tara Steffen,Mariah Hassert,E Taylor Stone,Brian T Grimberg,Stella G Hoft,Jianfeng Zhang,Amelia K Pinto,James D Brien,M Scot Roberts,Elizabeth Geerling

doi:10.3390/vaccines8020170

Tara Steffen, Mariah Hassert + Show 8 more

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https://doi.org/10.3390/vaccines8020170

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Abstract

Zika virus (ZIKV) is a significant public health concern due to the pathogen’s ability to be transmitted by either mosquito bite or sexual transmission, allowing spread to occur throughout the world. The potential consequences of ZIKV infection to human health, specifically neonates, necessitates the development of a safe and effective Zika virus vaccine. Here, we developed an intranasal Zika vaccine based upon the replication-deficient human adenovirus serotype 5 (hAd5) expressing ZIKV pre-membrane and envelope protein (hAd5-ZKV). The hAd5-ZKV vaccine is able to induce both cell-mediated and humoral immune responses to ZIKV epitopes. Importantly, this vaccine generated CD8+ T cells specific for a dominant ZIKV T cell epitope and is shown to be protective against a ZIKV challenge by using a pre-clinical model of ZIKV disease. We also demonstrate that the vaccine expresses pre-membrane and envelope protein in a confirmation recognized by ZIKV experienced individuals. Our studies demonstrate that this adenovirus-based vaccine expressing ZIKV proteins is immunogenic and protective in mice, and it encodes ZIKV proteins in a conformation recognized by the human antibody repertoire.

Highlights

Zika virus (ZIKV) is a re-emerging arbovirus of the Flavivirus genus that includes multiple important human pathogens including dengue viruses 1–4 (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and yellow fever virus (YFV) [1]
We investigated the potential for a protective and immunogenic human adenovirus serotype 5-based ZIKV vaccine based on the structural proteins prM and E with an E209A amino acid mutation that has been reported to improve the processing of the prM-E polypeptide [48]
The expression cassette containing the CMV promoter and tissue plasminogen activator (tPA)-ZIKV coding sequence was inserted into the E1 region of the human adenovirus serotype 5 (hAd5) vector where E1 and E3 had been deleted

Summary

Introduction

Zika virus (ZIKV) is a re-emerging arbovirus of the Flavivirus genus that includes multiple important human pathogens including dengue viruses 1–4 (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and yellow fever virus (YFV) [1]. Organization (WHO), a majority of individuals who are infected with ZIKV are asymptomatic, but those with a mild clinical form of the disease report symptoms including fever, rash, conjunctivitis, and muscle and joint pain, all of which typically last less than a week While these symptoms are rarely debilitating, complications of Zika virus disease can include Guillain–Barré syndrome. Zika-induced microcephaly and congenital abnormalities are generally classified as congenital Zika syndrome (CZS), which is a potential complication in the developing fetuses of pregnant women [4,6,7,8,9,10] These risks, combined with the explosive outbreaks that occurred at Yap Island in 2007 [11], French Polynesia in 2013 [12], and Brazil in 2015–16 [13], underscore the need to control the spread of ZIKV. There are no current FDA-approved vaccines available to control infection

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