Phenotypic and genetic characterization of a next generation live-attenuated yellow fever vaccine candidate.

We assessed the genetic and phenotypic characteristics of a yellow fever vaccine candidate, which was cloned from a YF-VAX substrain selected for growth in Vero cells (vYF-247), during the manufacturing process from the master seed lot (MSL) and working seed lot (WSL) through to the drug substance (DS) stage. There were nine minor nucleotide variants observed from the MSL to the DS stage, of which five led to amino acid changes. The variant positions were, however, not known risks for any virulence modification.

Next generation live-attenuated yellow fever vaccine candidate: Safety and immuno-efficacy in small animal models.

Yellow fever (YF) remains a threat to human health in tropical regions of Africa and South America. Live-attenuated YF-17D vaccines have proven to be safe and effective in protecting travellers and populations in endemic regions against YF, despite very rare severe reactions following vaccination - YF vaccine-associated viscerotropic disease (YEL-AVD) and neurological disease (YEL-AND). We describe the generation and selection of a live-attenuated YF-17D vaccine candidate and present its preclinical profile.

Chimeric yellow fever 17D-Zika virus (ChimeriVax-Zika) as a live-attenuated Zika virus vaccine.

Zika virus (ZIKV) is an emerging mosquito-borne pathogen representing a global health concern. It has been linked to fetal microcephaly and other birth defects and neurological disorders in adults. Sanofi Pasteur has engaged in the development of an inactivated ZIKV vaccine, as well as a live chimeric vaccine candidate ChimeriVax-Zika (CYZ) that could become a preferred vaccine depending on future ZIKV epidemiology.

Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials.

Two phase 3 placebo-controlled trials of the CYD-TDV vaccine, evaluated in children aged 2-14 y (CYD14) and 9-16 y (CYD15), demonstrated vaccine efficacy (VE) of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue (VCD).

Characterization of recombinant yellow fever-dengue vaccine viruses with human monoclonal antibodies targeting key conformational epitopes.

The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several dengue-endemic countries. Although the vaccine provides protection against dengue, the level of protection differs by serotype and warrants further investigation. We characterized the antigenic properties of each vaccine virus serotype using highly neutralizing human monoclonal antibodies (hmAbs) that bind quaternary structure-dependent epitopes.