Elevated understanding of the viral infection process contributes to development of neutralizing agents and vaccine to combat infectious diseases. Although crystal structure of single SARS-CoV-2 spike/RBD and host receptor ACE2 is known, the viral attachment and immune response initiated by numbers and distribution patterns of natural spikes on SARS-CoV-2 are still obscure. Leveraging a ~74 nm DNA soccer-ball framework (DSF), we developed an aptamer-guided SARS-CoV-2 RBD precisely assembly strategy, thereby exploring the viral infection and immune response in specific numbers and distributions of RBDs. Thirty evenly distributed RBDs on DSF could achieve sufficient binding affinity against host cell (Kd of 122.2 pM), whereas 60 evenly distributed RBDs on DSF could bind to host cell rapidly (Ka of 0.845 min-1). While RBDs in centralized manner compared to evenly distribution facilitated higher and faster binding to host. Moreover, evenly distributed 20 RBDs on DSF achieved up to 88% immunity elicitation of macrophage cells. Overall, this strategy provides a prospective direction for the assembly of virus-like particles based on DNA origami, thereby facilitating understanding of viral infection and efficient vaccine design.