Therapeutic Area: Production of monospecific polyclonal nanoantibodies
Nanoantibodies are a type of therapeutic protein with low molecular weight and high specificity against a specific target. They have structural properties that give it stability against conventional antibodies, broadening its route of administration, production, logistics, etc. Polyclonal nanoantibodies can be obtained from the immunization of camelids, while monoclonal nanoantibody sequences can be cloned from lymphocytes (obtained from the same camelids) using Phague Display Technology.
The COVID emergency and the availability of llamas and alpacas in northern Argentina facilitated the production and purification of monospecific anti-RBD polyclonal nanoantibodies against SARS-COV-2. These nanoantibodies were generated by immunizing llamas with the receptor-binding domain (RBD) of SARS-COV-2.
The promoted project generated an efficient protocol to produce SARS-CoV-2 RBD from human cell cultures. This was achieved by transducing cells lines with a lentivirus containing the genetic sequence of RBD. This produced a stable line of RBD-producing HEK-293 cells.
The RBD present in the culture media was purified and tested in llamas during an immunization plan. Antibody production was controlled by exploratory blood extractions and quantified by an ELISA test developed in-house.
Methodology was developed for testing the amount of anti-RBD antibodies produced and purifying them from immunized llama plasma. The purified antibodies were shown to have a neutralizing capacity against SARS-CoV-2 in pseudo virus neutralization assays.
This project is complementary to other recently published developments. Hyperimmune equine serum (developed by other ventures) has demonstrated therapeutic efficiency in clinical trials against COVID-19, when administered early, through intravenous administration. The SkyBio-supported nanoantibodies generated in camelids are polyclonal and can be enzymatically humanized to avoid adverse immune reactions upon administration in patients. The nanoantibody project is similar to the hyperimmune equine serum in that they both rely on polyclonal antibodies. However, nanoantibodies are of much smaller size, which allow them to be administered by nebulization or intranasally.