Development of Sanofi Pasteur tetravalent dengue vaccine.

R&D Dengue Vaccine Program Head, Sanofi Pasteur, Lyon, France.
Revista do Instituto de Medicina Tropical de São Paulo (Impact Factor: 0.91). 10/2012; 54 Suppl 18:15-7. DOI: 10.1590/S0036-46652012000700007
Source: PubMed
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    ABSTRACT: Recent efforts to combat the growing global threat of dengue disease, including deployment of phase IIb vaccine trials, has continued to be hindered by uncertainty surrounding equitable immune responses of serotypes, relative viral fitness of vaccine vs naturally occurring strains, and the importance of altered immune environments due to natural delivery routes. Human infection models can significantly improve our understanding of the importance of certain phenotypic characteristics of viral strains, and inform strain selection and trial design. With human models, we can further assess the importance of the natural delivery route of DENV and/or the accompanying mosquito salivary milieu. Accordingly, we discuss the use of mosquitoes in such a human infection model with DENV, identify important considerations, and make preliminary recommendations for deployment of such a mosquito improved DENV human infection model (miDHIM).
    The Journal of Infectious Diseases 06/2014; 209 Suppl 2:S71-8. DOI:10.1093/infdis/jiu110 · 5.78 Impact Factor
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    ABSTRACT: The incidence of dengue has been on the rise since at least the 1960s, bringing greater urgency to the need for a vaccine to prevent the disease. Recent advances suggest that the scientific world is moving closer to an effective dengue vaccine. However, there are concerns that the price of a future vaccine could limit its uptake. High prices, in addition to other challenges, have already weighed negatively in government decisions to include other new vaccines in national immunization programs, e.g., the pneumococcal, rotavirus, and human papillomavirus vaccines. Recent research on the value of vaccination, however, suggests that vaccination confers benefits that are often neglected by traditional economic evaluations. In the case of dengue, commonly overlooked benefits are likely to include reduced spending on outbreak control, averted losses in tourism flows, and avoided productivity losses due to long-term dengue sequelae. Accounting for these and other broader benefits of dengue vaccination could reveal significantly greater economic value and strengthen the case for inclusion of dengue vaccination in national immunization programs. In this article we discuss a framework for the broader value of vaccination and review its application in the context of dengue vaccination for Brazil.
    Seminars in Immunology 07/2013; DOI:10.1016/j.smim.2013.04.010 · 6.12 Impact Factor
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    ABSTRACT: An effective dengue vaccine should elicit immune responses against all four different dengue virus serotypes. This study optimized the codon usage of a gene encoding consensus dengue virus envelope protein domain III (cEDIII) with cross-neutralizing activity against four dengue virus serotypes for plant expression. Then, a plant expression vector was constructed with this gene under the control of the rice amylase 3D promoter (RAmy3D), which is a strong inducible promoter under sugar starvation conditions. The synthetic cEDIII gene was fused with the RAmy3D signal peptide and ER retention signal, SEKDEL, and was introduced into rice callus by particle bombardment-mediated transformation. The integration and expression of cEDIII gene in transgenic rice callus was confirmed by genomic DNA PCR amplification, Northern blot analysis, and western blot analysis, respectively. Densitometric analysis determined that the highest expression level of the cEDIII protein in lyophilized rice callus was approximately 0.45 mg g−1. These results suggest that it is feasible to use transgenic rice callus to produce the consensus dengue virus envelop protein domain III for edible vaccine purposes.
    Plant Cell Tissue and Organ Culture 06/2012; 109(3). DOI:10.1007/s11240-012-0116-y · 2.61 Impact Factor


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