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GLOBHELS-Global helse

Expression and evaluation of envelope domain III-based experimental tetravalent dengue vaccine using tobacco chloroplast expression system

Awarded: NOK 9.9 mill.

Project Number:

192510

Application Type:

Project Period:

2009 - 2015

Funding received from:

Subject Fields:

Partner countries:

Results from the whole project period (Oct 2009-June 2014) Background: Dengue viruses are mosquito-borne human pathogens with a worldwide prevalence. There are four different dengue virus serotypes, DEN-1 to DEN-4, which cause serious problems of morbidity and mortality. Dengue is emerging rapidly and there is still no effective dengue vaccine available. Objectives: This project aims to explore the possibility to produce dengue vaccine in an economic manner by using plants. We have chosen tobacco and lettuce as our green factories. The advantages of using tobacco are because (1) tobacco is a non-food, non-feed crop with large biomass; (2) there is no investment other than a greenhouse; (3) it is cheaper and easily implemented in developing countries; (4) a better use of tobacco plants for improvement of human health. We use lettuce, an ideal edible crop for the production of dengue vaccine with oral delivery significantly reducing the production costs. Results: Both crops are feasible for vaccine production and we have over the past four years completed our objectives and produced dengue vaccine antigens in tobacco and lettuce. These antigens are currently being tested on mice. This ?proof of concept? project has thus fulfilled its objectives and has generated results ranging from methodology development, scientific publications, reports, invited talks and oral presentations at conferences, and posters, to a PhD dissertation, a patent application and two new projects as a positive spin-off effect. We have followed our objectives and carried out the defined project activities and milestones. During the whole project period, the project team has produced: (a) 10 peer-reviewed scientific publications; (b) 1 patent application; (c) 1 PhD thesis; (d) 2 master?s theses; (e) 8 popular science publications; (f) 37 invited talks, oral and poster presentations at national and international conferences and (g) 6 media releases. Spin-off effect and impact: With our expertise and the strong national and international networks that we have developed during the project period, this GLOBVAC-financed project has generated significant positive spin-off effects with two newly funded projects on plant produced human- and fish (salmon) vaccines: an EEA Romania- Norway project (2014-2017) with Dr Jihong Liu Clarke as the project manager from the Norwegian side and a NFR Nano2021 programme financed project (2014-2017) where Dr Jihong Liu Clarke is the leader of workpackage (WP)1. This GLOBVAC project has paved the road for the sustainable development of a Norwegian plant-vaccine production platform. The two new spin-off projects have proven the importance of the GLOBVAC program funding and the success of this NFR-GLOBVAC funded project.

Dengue viruses (Flavivirus) are mosquito-borne human pathogens with a worldwide prevalence. There are four antigenically-related dengue virus serotypes, DEN-1 to DEN-4, which can cause serious problems of morbidity and mortality. Dengue is emerging rapidl y as one of the most important public health problems in countries of the Asia-Pacific region with nearly 1.8 billion people in the region at risk, compared to an estimated total of 2.5 billion globally (WHO 2007). In India, dengue is now re-emerging as o ne of the most important health problems with many outbreaks reported in different parts of the country during the past decade. The disease has resulted in widespread social and economic problems, especially among the poor who are the most vulnerable grou p. The lack of a dengue vaccine and antiviral drug makes it difficult for governments to control and manage the disease, although considerable efforts have been made, including vector control, sanctions, law enforcement and public education. To develop a vaccine against dengue infection and to establish a cost-effective system for large scale production of dengue vaccine(s) is important. We propose therefore an Indo-Norwegian project to (1) develop a cost-effective and safe production system for dengue va ccine via a tobacco chloroplast expression system and (2) produce a tetravalent vaccine against dengue by expressing the host cell receptor binding dengue envelope domain III of the four antigenic serotypes alone or together in tobacco chloroplasts. The f unctionality of the chloroplast-derived tetravalent dengue vaccine and the economic and social benefits of the chloroplast expression approach will be evaluated. All the proposed work will be conducted jointly by Norwegian and Indian partners and with the participation of an Austrian collaborator. This initiates our long-term collaboration on vaccine development and a cost-effective plant-based production system.

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Funding scheme:

GLOBHELS-Global helse