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Vaccines 2015, 3(3), 503-518; doi:10.3390/vaccines3030503

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

School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA
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Academic Editors: Annelies Wilder-Smith and Eng Eong Ooi
Received: 12 May 2015 / Revised: 18 June 2015 / Accepted: 30 June 2015 / Published: 3 July 2015
(This article belongs to the Special Issue Dengue Vaccines)
View Full-Text   |   Download PDF [230 KB, uploaded 3 July 2015]   |  

Abstract

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. View Full-Text
Keywords: measles vectors; HBsAg subviral particles; dengue vaccine platform measles vectors; HBsAg subviral particles; dengue vaccine platform
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Harahap-Carrillo, I.S.; Ceballos-Olvera, I.; Valle, J.R.-D. Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus. Vaccines 2015, 3, 503-518.

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