Current vaccines to protect against SARS-CoV-2 rely on the immunogenicity conferred by the viral Spike protein, the main viral target against which the elicitation of neutralizing and protective antibodies is intended through vaccination.
The Spike presents an extremely high affinity for the human ACE-2 (Angiotensin Converting Enzyme-2) receptor, which has been reported to be expressed in diverse layers of the organism, such as the epidermis, endothelium, muscle and sweat glands.
Such a strong affinity between both proteins, the Spike and ACE-2, might lead to the retention of the immunogen and a suboptimal distribution to reach the lymph nodes, key for a robust immune response. Thus, we propose modifications in the SARS-CoV-2 Spike vaccine protein that reduces the affinity for ACE-2 while preserving key epitopes for elicitation of neutralizing antibodies. This technology lies in minimal modifications of the Spike protein sequences that reduce ACE-2 binding, leading to the aforementioned proposed advantages at the immunological level in this new vaccination strategy.
To date, accurate biochemical experiments to show a reduced ACE-2 binding capacity for our vaccine candidates have been carried out to demonstrate the viability of the proposed solution, the results of which have been surprising in terms of confirming the initial hypothesis.
1. Potentiation of the immune response via vaccination.
2. Enhance generation of neutralizing antibodies.
3. Increased safety, as the immunogen will reduce its binding capacity to a natural host receptor.
The next step will assess the potential of our new vaccine candidates in experimental in vivo models. These experiments need to be carried out to confirm the feasibility and the good results demonstrated in vitro, to advance with the development of the product together with a company that licensees the technology later on.
Jacinto López-Sagaseta, Gilda Dichiara Rodríguez, Elena Erausquin Arrondo.
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