Shortly after SARS-CoV emerged at the turn of the 21st century, the spike (S) protein (particularly in its prefusion [native] conformation) was identified as the immunodominant antigen of the virus. 1 Evaluation of patients with SARS-CoV-2 revealed that binding and neutralizing antibodies primarily target the receptor-binding domain of the S1 subunit. 2 Once this putative vaccine target was identified, the next challenge was how to best generate an effective immune response to SARS-CoV-2. The characteristics of this response would include production of neutralizing antibodies, generation of a T-cell response, and avoidance of immune-enhanced disease (vaccine-induced response that led to paradoxically increased disease severity on viral challenge).