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Open AccessArticle

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