Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana
Dengue fever is currently ranked as the top emerging tropical disease, driven by increased global travel, urbanization, and poor hygiene conditions as well as global warming effects which facilitate the spread of Aedes mosquitoes beyond their current distribution. Today, more than 100 countries are...
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doaj-8b169e1df4774f27af21d3ef71ae01a82020-11-25T00:41:03ZengFrontiers Media S.A.Frontiers in Plant Science1664-462X2019-04-011010.3389/fpls.2019.00455440378Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamianaEe Leen Pang0Hadrien Peyret1Alex Ramirez2Hwei-San Loh3Kok-Song Lai4Chee-Mun Fang5William M. Rosenberg6George P. Lomonossoff7School of Biosciences, University of Nottingham Malaysia, Semenyih, MalaysiaDepartment of Biological Chemistry, John Innes Centre, Norwich, United KingdomiQur Limited, London, United KingdomSchool of Biosciences, University of Nottingham Malaysia, Semenyih, MalaysiaFaculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, MalaysiaDivision of Biomedical Sciences, School of Pharmacy, University of Nottingham Malaysia, Semenyih, MalaysiaiQur Limited, London, United KingdomDepartment of Biological Chemistry, John Innes Centre, Norwich, United KingdomDengue fever is currently ranked as the top emerging tropical disease, driven by increased global travel, urbanization, and poor hygiene conditions as well as global warming effects which facilitate the spread of Aedes mosquitoes beyond their current distribution. Today, more than 100 countries are affected most of which are tropical Asian and Latin American nations with limited access to medical care. Hence, the development of a dengue vaccine that is dually cost-effective and able to confer a comprehensive protection is ultimately needed. In this study, a consensus sequence of the antigenic dengue viral glycoprotein domain III (cEDIII) was used aiming to provide comprehensive coverage against all four circulating dengue viral serotypes and potential clade replacement event. Utilizing hepatitis B tandem core technology, the cEDIII sequence was inserted into the immunodominant c/e1 loop region so that it could be displayed on the spike structures of assembled particles. The tandem core particles displaying cEDIII epitopes (tHBcAg-cEDIII) were successfully produced in Nicotiana benthamiana via Agrobacterium-mediated transient expression strategy to give a protein of ∼54 kDa, detected in both soluble and insoluble fractions of plant extracts. The assembled tHBcAg-cEDIII virus-like particles (VLPs) were also visualized from transmission electron microscopy. These VLPs had diameters that range from 32 to 35 nm, presenting an apparent size increment as compared to tHBcAg control particles without cEDIII display (namely tEL). Mice immunized with tHBcAg-cEDIII VLPs showed a positive seroconversion to cEDIII antigen, thereby signifying that the assembled tHBcAg-cEDIII VLPs have successfully displayed cEDIII antigen to the immune system. If it is proven to be successful, tHBcAg-cEDIII has the potential to be developed as a cost-effective vaccine candidate that confers a simultaneous protection against all four infecting dengue viral serotypes.https://www.frontiersin.org/article/10.3389/fpls.2019.00455/fullvirus-like particlesepitope displayhepatitis B core antigendengue envelope glycoproteinenvelope glycoprotein domain IIIdengue vaccine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ee Leen Pang Hadrien Peyret Alex Ramirez Hwei-San Loh Kok-Song Lai Chee-Mun Fang William M. Rosenberg George P. Lomonossoff |
spellingShingle |
Ee Leen Pang Hadrien Peyret Alex Ramirez Hwei-San Loh Kok-Song Lai Chee-Mun Fang William M. Rosenberg George P. Lomonossoff Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana Frontiers in Plant Science virus-like particles epitope display hepatitis B core antigen dengue envelope glycoprotein envelope glycoprotein domain III dengue vaccine |
author_facet |
Ee Leen Pang Hadrien Peyret Alex Ramirez Hwei-San Loh Kok-Song Lai Chee-Mun Fang William M. Rosenberg George P. Lomonossoff |
author_sort |
Ee Leen Pang |
title |
Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana |
title_short |
Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana |
title_full |
Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana |
title_fullStr |
Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana |
title_full_unstemmed |
Epitope Presentation of Dengue Viral Envelope Glycoprotein Domain III on Hepatitis B Core Protein Virus-Like Particles Produced in Nicotiana benthamiana |
title_sort |
epitope presentation of dengue viral envelope glycoprotein domain iii on hepatitis b core protein virus-like particles produced in nicotiana benthamiana |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Plant Science |
issn |
1664-462X |
publishDate |
2019-04-01 |
description |
Dengue fever is currently ranked as the top emerging tropical disease, driven by increased global travel, urbanization, and poor hygiene conditions as well as global warming effects which facilitate the spread of Aedes mosquitoes beyond their current distribution. Today, more than 100 countries are affected most of which are tropical Asian and Latin American nations with limited access to medical care. Hence, the development of a dengue vaccine that is dually cost-effective and able to confer a comprehensive protection is ultimately needed. In this study, a consensus sequence of the antigenic dengue viral glycoprotein domain III (cEDIII) was used aiming to provide comprehensive coverage against all four circulating dengue viral serotypes and potential clade replacement event. Utilizing hepatitis B tandem core technology, the cEDIII sequence was inserted into the immunodominant c/e1 loop region so that it could be displayed on the spike structures of assembled particles. The tandem core particles displaying cEDIII epitopes (tHBcAg-cEDIII) were successfully produced in Nicotiana benthamiana via Agrobacterium-mediated transient expression strategy to give a protein of ∼54 kDa, detected in both soluble and insoluble fractions of plant extracts. The assembled tHBcAg-cEDIII virus-like particles (VLPs) were also visualized from transmission electron microscopy. These VLPs had diameters that range from 32 to 35 nm, presenting an apparent size increment as compared to tHBcAg control particles without cEDIII display (namely tEL). Mice immunized with tHBcAg-cEDIII VLPs showed a positive seroconversion to cEDIII antigen, thereby signifying that the assembled tHBcAg-cEDIII VLPs have successfully displayed cEDIII antigen to the immune system. If it is proven to be successful, tHBcAg-cEDIII has the potential to be developed as a cost-effective vaccine candidate that confers a simultaneous protection against all four infecting dengue viral serotypes. |
topic |
virus-like particles epitope display hepatitis B core antigen dengue envelope glycoprotein envelope glycoprotein domain III dengue vaccine |
url |
https://www.frontiersin.org/article/10.3389/fpls.2019.00455/full |
work_keys_str_mv |
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