By Dr. Liji Thomas, MDNov 2 2022Reviewed by Aimee Molineux The world has recently seen immense activity in the field of vaccine development due to the coronavirus disease 2019 pandemic, as the causative virus, the severe acute respiratory syndrome coronavirus 2 , continues to emerge in new variants with increased transmissibility, immune escape capability and virulence attributes.
These antibodies need to be given intravenously, necessitating a medical setting. They must be delivered in relatively large doses of 10–100 mg kg−1 to compensate for the fact that only a small fraction reaches the site of interest. This drives up the cost of treatment, limiting their availability, especially in low- and middle-income countries .
Earlier research by the same authors showed the capability to direct mRNA to the lungs to produce mAbs there. By avoiding the need to introduce the recombinant spike protein, the researchers encoded a membrane anchor in the heavy chain of the immunoglobulin G antibody molecule. This allowed the tissue to retain the antibody for several weeks.
Related StoriesDirect stochastic optical reconstruction microscopy enhanced the ability to view the antibodies once expressed within the cell culture. One formed long strings on the cell surface and was thus disqualified from further testing in vivo. Longer retention in lungs This demonstrated that the antibodies were, as expected, anchored to the cell membrane in the lung by the GPI molecule. Compared with the secreted or non-anchored form, it was found to remain in the lung tissue. At the same time, the latter led to increased serum concentrations, the difference in post-transfection serum levels being 27-fold in favor of the secreted form.
Since the virus is mostly found within the alveolar space, this finding indicates the potential for transfected antibodies to prevent COVID-19 and severe disease. The effective dose delivered to the lungs can be enhanced by increasing the concentration of the formulation.