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The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain (RBD) multi-strain hybrid antigen is a bioengineered protein designed to elicit broad-spectrum immunity against multiple viral variants. This antigen typically combines structural elements or epitopes from several strains, such as the ancestral Wuhan-Hu-1, Delta, and Omicron variants, into a single chimeric or mosaic molecule (Cohen et al., Science 2022). The primary biological role of the RBD is to facilitate viral entry by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor, making it the most critical target for neutralizing antibodies (Walls et al., Cell 2020). By presenting a diverse array of RBD sequences, these hybrid antigens stimulate the production of antibodies that recognize conserved regions across different lineages, potentially providing protection against future variants. These antigens are primarily used in the development of next-generation vaccines, including protein subunit and nanoparticle-based platforms like VBI-2901 or GBP510 (VBI Vaccines 2021; SK Bioscience 2022). In clinical applications, they aim to overcome the limitations of monovalent vaccines, which often lose efficacy as the virus evolves. The interaction with the immune system involves both B-cell activation for antibody production and T-cell priming for long-term cellular memory. Monitoring the efficacy of these antigens involves measuring neutralizing antibody titers and ACE2 binding inhibition.
Elicitation of neutralizing antibodies that sterically hinder the interaction between the viral RBD and the host ACE2 receptor, thereby preventing viral entry into host cells.
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