Abstract
ObjectivesTo explore Saccharomyces cerevisiae as an expression platform for dengue oral immune complex vaccine development.ResultsMolecular engineering was applied to create a fusion gene construct (scEDIII-PIGS) consisting of a yeast codon optimized sequence encoding for a synthetic consensus dengue envelope domain III (scEDIII) followed by a modified IgG Fc domain (PIGS). Northern blot showed transcription of the target gene, with a temporal expression pattern similar to those from previous work. Western blot showed assembly of various immune complexes from monomer to hexamer. Partial purification of scEDIII-PIGS was also attempted to demonstrate the feasibility of yeast system for immune complex vaccine development. Approximately 1 mg of scEDIII-PIGS can be produced from 1 l culture.ConclusionThis work demonstrated for the first time that various immunocomplex structures of our target protein could be efficiently produced in S. cerevisiae for future application in developing oral and injectable vaccines against various pathogens.
Highlights
Dengue fever is a disease caused by mosquito-borne dengue virus and becomes a major global health crisis
This work demonstrated for the first time that various immunocomplex structures of our target protein could be efficiently produced in S. cerevisiae for future application in developing oral and injectable vaccines against various pathogens
We explored the possibility of using S. cerevisiae to produce an immunocomplex comprised of a synthetic consensus dengue envelope domain III conjugated with a murine Fc fragment from IgG2 (PIGS)
Summary
Dengue fever is a disease caused by mosquito-borne dengue virus and becomes a major global health crisis. Dengue viruses consist of four serotypes that are genetically distinct but highly similar (Katzelnick et al 2015). While infection with one dengue serotype confers life-time protection against that serotype, the most severe forms of dengue fever, dengue hemorrhage fever and dengue shock syndromes, are the result of secondary infection by heterologous serotypes, a process referred to as ‘‘antibody-dependent enhancement’’, (Balsitis et al 2010). A number of dengue vaccines are being developed, the molecular and immunological reasons behind poor performance are still being studied. Mucosal vaccines are vaccines that can be delivered nasally, orally, rectally or vaginally. Mucosal vaccines are cheaper, safer, and more appropriate for mass distribution than parenteral vaccines (Lycke 2012; Zeng 2016; Miquel-Clopes et al 2019)
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