Article

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: 1.01). 10/2012; 54 Suppl 18:15-7. DOI: 10.1590/S0036-46652012000700007
Source: PubMed

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    • "CYD-TDV has undergone extensive safety and immunogenicity assessment in dengue endemic and non-endemic populations [10] [11] [12] [13] [14] [15] [16] [17]. To fulfil the needs of phase III studies, the scale-up of CYD-TDV production has been undertaken in parallel with its clinical development [18]. Differences in the production of CYD-TDV lots used up to phase II and those used in phase III relate to the scale-up of the virus/cell culture. "
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    ABSTRACT: The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. Copyright © 2015. Published by Elsevier Ltd.
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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.
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    ABSTRACT: The Asia Pacific Pediatric Association Vaccinology Update 2010 (APPA VU 2010) was held in Mumbai on November 13-14, 2010. This second part of the conference report discusses the interesting information about vaccines which are expected in the near future, namely, live-attenuated Japanese encephalitis virus vaccine, tetravalent dengue virus vaccine, conjugate typhoid vaccine and conjugate meningococcal A vaccine.
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