These findings also indicate that it might be difficult to distinguish exposure to SARS-CoV-2 from other SARSr-CoVs in serological studies using S ectodomain trimers and that specific assays will need to be designed. The investigation results provide structural framework to identify conserved and accessible epitopes across S glycoproteins that will support ongoing vaccine design efforts. Elicitation of diverse, polyclonal Ab responses might prove key in light of the diversity of viruses circulating in animal reservoirs and in preventing the possible emergence of viral neutralization.