Immunogenicity and efficacy of a recombinant human adenovirus type 5 vaccine against zika virus

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

doi:10.3390/vaccines8020170

Immunogenicity and efficacy of a recombinant human adenovirus type 5 vaccine against zika virus

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

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English
Article number	170
Journal	Vaccines
Volume	8
Issue number	2
DOIs	https://doi.org/10.3390/vaccines8020170
State	Published - Apr 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Funding: This work was supported by National institutes of Health grant F31 AI152460–01 from the National Institute of Allergy and Infectious Diseases (NIAID) awarded to M.H. This research was funded by National Institute of Allergy and Infectious Diseases, K22AI104794 to J.D.B. and Saint Louis University startup funding to A.K.P. and J.D.B.

Funders	Funder number
National Institutes of Health (NIH)	F31 AI152460–01
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	K22AI104794
Saint Louis University

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Animal model
Immune response
Pre-clinical development
Zika virus vaccine

ASJC Scopus subject areas

Immunology
Pharmacology
Drug Discovery
Infectious Diseases
Pharmacology (medical)

Access to Document

10.3390/vaccines8020170

Cite this

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title = "Immunogenicity and efficacy of a recombinant human adenovirus type 5 vaccine against zika virus",

abstract = "Zika virus (ZIKV) is a significant public health concern due to the pathogen{\textquoteright}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.",

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author = "Tara Steffen and Mariah Hassert and Hoft, \{Stella G.\} and Stone, \{E. Taylor\} and Jianfeng Zhang and Elizabeth Geerling and Grimberg, \{Brian T.\} and Roberts, \{M. Scot\} and Pinto, \{Amelia K.\} and Brien, \{James D.\}",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = apr,

doi = "10.3390/vaccines8020170",

language = "English",

volume = "8",

number = "2",

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AU - Hoft, Stella G.

AU - Stone, E. Taylor

AU - Zhang, Jianfeng

AU - Geerling, Elizabeth

AU - Grimberg, Brian T.

AU - Roberts, M. Scot

AU - Pinto, Amelia K.

AU - Brien, James D.

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N2 - 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.

AB - 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.

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KW - Immune response

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Immunogenicity and efficacy of a recombinant human adenovirus type 5 vaccine against zika virus

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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