Elucidating the Effect of Nanoscale Receptor-Binding Domain Organization on SARS-CoV-2 Infection and Immunity Activation with DNA Origami

Multivalent display of SARS-CoV-2 RBDs (receptor-binding domains, prime proteins for viral infection and as vaccine immunogens) affects infectivity and as immunogens on a virus-like particle (VLP) can enhance immune response. However, the viral attachment and immune response initiated by the copy number and distribution pattern of SARS-CoV-2 RBDs remain poorly under-stood. Here, we organize SARS-CoV-2 RBDs on DNA nanoballs of similar to 74 nm diameter by an aptamer-guided assembly for a systematic interrogation. We find that both the affinity and the rate of the DNA-based VLP binding to the host cell increase with the RBD number (10-90). In addition, a concentrated RBD distribution promotes faster and stronger interaction to the host cell than an even RBD distribution. Moreover, it is interesting to learn that the immunity activation does not increase linearly with RBD numbers on the VLP. As few as 20 evenly distributed RBDs per VLP can elicit up to 86% immunity of macrophage cells. Overall, the work provides a new tool to study SARS-CoV-2 infection and VLP-based immunity activation, which should deepen our understanding of viral infection and facilitate the development of highly effective antiviral vaccines.

Automated summary

The number and distribution pattern of SARS-CoV-2 RBDs affect viral infection and immune response. Increasing the number of RBDs on a virus-like particle (VLP) enhances the binding affinity and rate to host cells. Concentrated distribution of RBDs promotes faster and stronger interaction with host cells. Interestingly, even a small number of evenly distributed RBDs on the VLP can elicit a high level of immune response.