by In response to the emergence of new SARS-CoV-2 virus variants that render current monoclonal antibodies ineffective, researchers have developed a potential solution. A team led by Professor Jan Terje Andersen has recently published a study in PNAS Nexus, outlining the development of a long-acting biologic with transmucosal transport properties that can neutralize the latest virus variants.
When the COVID-19 pandemic first began, there were no effective antiviral drugs available. However, the development of monoclonal antibodies proved to be a breakthrough in the fight against the disease. Unfortunately, these antibodies have now been rendered ineffective against the new virus variants due to mutations in the spike protein.
While vaccines offer protection against severe disease, there is still a pressing need for virus-blocking agents for therapeutic or prophylactic use, particularly for immunocompromised patients. These individuals have weakened immune systems due to medical conditions or immunosuppressive drug treatments. This includes individuals with severe primary immunodeficiency disease, organ or stem cell transplant recipients, and those undergoing cancer treatments such as CAR-T-cell therapy.
To meet this need, researchers are developing new monoclonal antibodies that can neutralize the latest virus variants by targeting their spike protein. However, there is a concern that these antibodies may lose their effectiveness as the virus continues to mutate and evolve, posing a significant challenge to their commercial development.
An alternative approach being explored is the use of soluble recombinant human angiotensin-converting enzyme 2 (ACE2) protein as a decoy receptor for SARS-CoV-2. ACE2 is the cellular receptor for the virus, and binding to ACE2 is necessary for infection to occur.
The challenge with soluble recombinant ACE2 is that it has a short plasma half-life of only 10 hours in humans, which is suboptimal when both systemic and mucosal tissue presence is required.
In their study, Professor Andersen’s team developed a tailored ACE2 biologic by fusing ACE2 to an engineered human albumin variant. Albumin binds to a cellular receptor called FcRn, which is widely expressed in mucosal epithelial cells and endothelial cells lining blood vessels. FcRn protects albumin from degradation, thereby extending its plasma half-life.
The designed albumin variant exhibited strong binding to human FcRn, leading to an even longer plasma half-life for the ACE2 fusion proteins. Moreover, FcRn expressed on mucosal epithelial cells facilitated the non-invasive transport of the fusion protein into the body. The engineered ACE2 also demonstrated enhanced binding to the spike protein, resulting in the biologic’s potent ability to block cellular infection by all tested SARS-CoV-2 variants.
Understanding the complex biology of FcRn opens up opportunities for designing biologics with improved pharmacokinetic properties and selective delivery across various barriers in the body. The long-acting and pan-SARS CoV-2 specific soluble ACE2 biologic developed in this study holds promise for prophylactic or therapeutic use in immunocompromised patients, according to Professor Jan Terje Andersen, the senior author of the study.
In conclusion, this innovative approach utilizing a long-acting biologic with transmucosal transport properties shows potential in combating SARS-CoV-2 virus variants. Further research and exploration are needed to fully evaluate its efficacy and determine its suitability for therapeutic or prophylactic use in immunocompromised patients.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemicals and materials, defense and aerospace, consumer goods, etc.
