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As the world continues to adapt to the new normal brought by the COVID-19 pandemic, biotechnological companies, research institutions and governments continue working tirelessly towards developing effective vaccines for COVID-19.

Ascendo Biotechnology Company and Academia Sinica in Taiwan announced the development of a new COVID-19 vaccine candidate in September. Named ASD25X-RBD, this new candidate has demonstrated potential as an effective vaccine in preclinical animal tests.

ASD25X-RBD works by promoting the production of antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the angiotensin-converting enzyme 2 (ACE2) cell receptor.

To help us better understand what this means, let us first take a look at how SARS-CoV-2 causes an infection. The ACE2 cell receptor is a protein found on the surface of many cell types, and whose normal function is breaking up large angiotensinogen proteins that then regulate cell functions. ACE2 therefore plays a major role in the renin-angiotensin-aldosterone system (RAAS) pathway that regulates blood pressure, wound healing and inflammation.

However, SARS-CoV-2 makes use of this commonly found cell receptor to make its entry into cells. The spike-like protein on the surface of SARS-CoV-2 contains a specific RBD, which binds to ACE2. This interaction triggers the fusion of cell and viral membranes, allowing the virus to enter the cell.

Dr Tao Mi-Hua and his team from the Institute of Biomedical Sciences of Academia Sinica developed ASD25X-RBD by identifying the RBD of the spike-like protein receptor of SARS-CoV-2 bound to ACE2. The vaccine candidate was built on the ASD25X technology platform, which was first developed by the lab of Associate Professor Chen Yu-Hong at the National Cheng Kung University College of Medicine.

ASD25X-RBD is a recombinant vaccine comprising segments of the RBD of the spike-like protein of SARS-CoV-2 which binds ACE2. By inducing the production of serum anti-RBD antibodies, it prevents the virus from binding to ACE2 and infecting cells.

Instead of targeting the spike-like protein, ASD25X-RBD targets the unmodified RBD region, which has extremely high genetic stability. This provides a number of advantages over other vaccine candidates. Firstly, the genetic stability of the RBD means that it is more likely to be retained even if the virus mutates or evolves. Secondly, using an unmodified RBD as an antigen means that fermentation production can be used to manufacture large volumes of the antigen quickly, which is useful for mass vaccine production.

Encouragingly, ASD25X-RBD has performed well in animal tests. Dr Tao Mihua and his team used the adeno-associated virus (AAV) to promote the expression of ACE2 in mice, producing AAV/ACE2 mice which are able to closely simulate COVID-19 infections in humans. Administration of ASD25X-RBD was found to effectively prevent infection by SARS-CoV-2, as infectious viral particles were not detected in the lungs of 100 percent of the treated mice.

The research team also demonstrated that treating Vero E6 cells with ASD25X-RBD effectively prevents their infection by SARS-CoV-2. Vero E6 cells are the most widely used cell line for replication and isolation of the SARS-CoV-2 virus, due to their high expression of ACE2. Therefore, these findings suggest that ASD25X-RBD is indeed able to prevent the binding interaction between the virus and the ACE2 cell receptors, thus preventing the entry of SARS-CoV-2 into cells and subsequent infections.

Following these successful findings, Ascendo Biotechnology Company plans to submit applications for clinical trials to further explore the potential of ASD25X-RBD as a vaccine candidate for COVID-19. They are hopeful that ASD25X-RBD could have the potential to provide complete immune protection against SARS-CoV-2, in addition to having massive production scalability. [APBN]