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The spike (S) glycoprotein of the coronavirus SARS-CoV-2 is responsible for viral entry into human cells by directly binding the angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface by many cell types. Consequently, it has been the major target for the development of antibodies, entry inhibitors, and vaccines. The S protein is a homotrimeric fusion protein, each consisting of two functional subunits, S1 and S2, facilitating the attachment and the fusion to the cell membrane, respectively. The N- and C-terminal regions of the S1 subunit fold into two distinct domains where the latter harbors the ACE2 receptor-binding domain (RBD). Various forms of the S protein are currently being explored as vaccine antigens to elicit humoral responses by the immune system. Understanding such responses induced by these different antigens is essential for the development of an effective vaccine for the prevention of COVID-19, the disease caused by the virus.
Recently, Ravichandran, S. et al. reported a comprehensive study of antibody responses in rabbits immunized with various S protein antigens: the S-ectodomain (S1+S2) (aa 16-1213), the S1 subunit (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 subunit (aa 686-1213). These antigens were produced in either mammalian or insect cells, and the purified antigens were mixed with Emulsigen adjuvant and injected into female New Zealand white rabbits intramuscularly twice with a 14-day interval; pre-vaccination sera and 8-day post-vaccination sera were collected and analyzed through several bioanalytical methods, including the enzyme linked immunosorbent assay, RBD competition assay, surface plasmon resonance, and neutralization assay. The assay results revealed that all three antigens, not S2, induced strong neutralizing antibodies, with the RBD eliciting a higher antibody titer with a 5-fold higher affinity, and that there was a strong correlation between antibody affinity and neutralization titer. The researchers also identified immunodominant epitopes via the analysis of vaccination-induced antibody repertoires using phage-display libraries of the SARS-CoV-2 spike genome fragment. The analysis revealed that the antibody repertoire induced by the recombinant RBD bound the largest number of phages, with regions highly concentrated around the RBD / receptor binding motif (RBM), and that several of these regions were found to be exposed on the surface of the native prefusion spike.
In conclusion, this study highlights the importance of evaluating different antigen options for their potentials to elicit strong immune responses when developing a vaccine as well as provides guidance for the rational design and development of an effective vaccine or therapeutic against COVID-19.
Note: Note: GenScript is proud to be the synthesizer of the SARS-CoV-2 spike glycoprotein gene for this study. We additionally offer ready-to-ship gram-level SARS-CoV-2 protein antigens, as well as over 50 SARS-CoV-2 control reagent mAbs available on demand (including high-affinity rabbit mAbs, and neutralizing mAbs)!