Abstract:
Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention
for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However,
a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb
preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing
encapsulated cell system. Methods: Murine G-8 myoblasts were transfected with plasmids coding
for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the
Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The
microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and
changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the
mAb was performed using western blotting, RBD ELISA, and microscopy. Results: Transfected
G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell
encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably
secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a
gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656–2190] ng/mL
and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an
increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation
showed a reduced per-microcapsule mAb production. Summary: We demonstrate here that cell
microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with
potential therapeutic applications that warrant further exploration.