Development of a capillary zone electrophoresis method for dose determination in a tetravalent dengue vaccine candidate.

Dengue is known to cause morbidity and mortality worldwide and currently there is neither available specific therapeutics to treat nor a vaccine to prevent this disease. Although efforts are being made, development of a vaccine against this disease remains challenging. Hawaii Biotech Inc developed a recombinant subunit envelope protein-based vaccine against all four serotypes produced in Drosophila S2 cells which were transferred over to Merck in 2010. Each subunit of the four dengue serotypes contains the N-terminal 80% of the amino acids comprising the envelope protein (DEN-80E). A Phase 1 study using only monovalent DEN1-80E was done by Hawaii Biotech Inc and most recently, a Phase 1 clinical trial of the tetravalent DEN-80E formulation (V180) was conducted. Here, we report the development of a dose assay for the tetravalent dengue vaccine-containing subunit protein of DEN1-80E, DEN2-80E, DEN3-80E, and DEN4-80E using various separation methods such as HPLC and CE. Based on the results of the comparison, the CZE separation was chosen as the most suitable method to perform the dose assay for the tetravalent dengue vaccine.