In a recent international project, it was demonstrated that MiCAN’s immortalised myeloid cells derived from human iPSC (Mylc) as used as human dendritic cells (DCs) worked with dengue virus (DEVN) better than conventional cells like Vero and K562.
DENV is one of the most important mosquito-borne viruses and is the causative agent of dengue and severe dengue. An estimated 390 million DENV infections occur annually in humans, with approximately 100 million infected individuals exhibiting clinical symptoms, such as high fever, muscle and joint pains, headache, rash, etc. Development of DENV vaccine has been carried out by many international researchers, however, there are still no blockbuster type of vaccine launched with confirming the effectiveness and the safety. There is a commercially available vaccine developed by a mega-pharma, however, it was confirmed to cause severe diseases among younger seronegative vaccinees though partially work in protecting seropositive vaccine recipients from severe disease.
One of the reasons of the difficulty to develop the vaccine is caused by the antibody-dependent enhancement, or ADE, which enhances viral entry via Fc gamma receptors, is one of the pathogenic mechanisms increasing disease sensitivity. This means that ADE should not be induced by the cells used in the basic research too. Further background information is available from the publication.
“iPS-ML” and “iPS-DC” (immature and differentiated DC accordingly, both commercially available as Mylc cell product from MiCAN) are more susceptible to DENV compared with Vero and K562.
(B - left) ADE activities in human sera from three individuals were detected on iPS-ML, iPS-DC and K562 cells. As a negative control, iPS-ML, iPS-DC or K562 cells were infected with DENV-4 in the absence of any sera (No-serum). The viral titer in the undiluted supernatant was determined by culture on Vero cells followed by immunostaining with ABC reagent. (C - right) Dose-dependent ADE activity curves of three human sera against DENV-4. Infective titers in the culture supernatant from Figure 2B were determined by focus-forming assay on Vero cells. ADE activity was expressed as the fold enhancement.
MiCAN is a world leading technical company being able to control the differentiation processes from human stem cells (iPS/ES) to dendritic cells (DCs) with also being able to immortalize the cells before the maturation (patented technology). This technology can be applied for many drug discovery fields especially requiring high susceptibility such as ADE controls. This technology is now applied for COVID-19 vaccine development too.
MiCAN’s platform technology
Dengue virus susceptibility in novel immortalized myeloid cells.
Atsushi Yamanaka , Kazuo Miyazaki , Jun Shimizu , Satoru Senju
Heliyon, Issue: 11, Volume: 6, Nov 3, 2020
Top image: CDC (Centers for Disease Control and Prevention)