Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus

Vaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 envelope protei...

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Main Authors: Indira S. Harahap-Carrillo, Ivonne Ceballos-Olvera, Jorge Reyes-del Valle
Format: Article
Language:English
Published: MDPI AG 2015-07-01
Series:Vaccines
Subjects:
Online Access:http://www.mdpi.com/2076-393X/3/3/503
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author Indira S. Harahap-Carrillo
Ivonne Ceballos-Olvera
Jorge Reyes-del Valle
author_facet Indira S. Harahap-Carrillo
Ivonne Ceballos-Olvera
Jorge Reyes-del Valle
author_sort Indira S. Harahap-Carrillo
collection DOAJ
description Vaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 envelope protein (E), which contains epitopes that elicits highly specific neutralizing antibodies. We modified the hepatitis B small surface antigen (HBsAg, S) in order to display DV 2 DIII on a virus-like particle (VLP), thus generating the hybrid antigen DIII-S. Two varieties of measles virus (MV) vectors were developed to express DIII-S. The first expresses the hybrid antigen from an additional transcription unit (ATU) and the second additionally expresses HBsAg from a separate ATU. We found that this second MV vectoring the hybrid VLPs displaying DIII-S on an unmodified HBsAg scaffold were immunogenic in MV-susceptible mice (HuCD46Ge-IFNarko), eliciting robust neutralizing responses (averages) against MV (1:1280 NT90), hepatitis B virus (787 mIU/mL), and DV2 (1:160 NT50) in all of the tested animals. Conversely, the MV vector expressing only DIII-S induced immunity against MV alone. In summary, DV2 neutralizing responses can be generated by displaying E DIII on a scaffold of HBsAg-based VLPs, vectored by MV.
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spelling doaj.art-6814fc16f2614d86845cc2219cc632002022-12-22T03:59:20ZengMDPI AGVaccines2076-393X2015-07-013350351810.3390/vaccines3030503vaccines3030503Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles VirusIndira S. Harahap-Carrillo0Ivonne Ceballos-Olvera1Jorge Reyes-del Valle2School of Life Sciences, Arizona State University, Tempe, AZ 85281, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85281, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85281, USAVaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 envelope protein (E), which contains epitopes that elicits highly specific neutralizing antibodies. We modified the hepatitis B small surface antigen (HBsAg, S) in order to display DV 2 DIII on a virus-like particle (VLP), thus generating the hybrid antigen DIII-S. Two varieties of measles virus (MV) vectors were developed to express DIII-S. The first expresses the hybrid antigen from an additional transcription unit (ATU) and the second additionally expresses HBsAg from a separate ATU. We found that this second MV vectoring the hybrid VLPs displaying DIII-S on an unmodified HBsAg scaffold were immunogenic in MV-susceptible mice (HuCD46Ge-IFNarko), eliciting robust neutralizing responses (averages) against MV (1:1280 NT90), hepatitis B virus (787 mIU/mL), and DV2 (1:160 NT50) in all of the tested animals. Conversely, the MV vector expressing only DIII-S induced immunity against MV alone. In summary, DV2 neutralizing responses can be generated by displaying E DIII on a scaffold of HBsAg-based VLPs, vectored by MV.http://www.mdpi.com/2076-393X/3/3/503measles vectorsHBsAg subviral particlesdengue vaccine platform
spellingShingle Indira S. Harahap-Carrillo
Ivonne Ceballos-Olvera
Jorge Reyes-del Valle
Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
Vaccines
measles vectors
HBsAg subviral particles
dengue vaccine platform
title Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
title_full Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
title_fullStr Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
title_full_unstemmed Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
title_short Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus
title_sort immunogenic subviral particles displaying domain iii of dengue 2 envelope protein vectored by measles virus
topic measles vectors
HBsAg subviral particles
dengue vaccine platform
url http://www.mdpi.com/2076-393X/3/3/503
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