evidence: Most candidate COVID-19 vaccines are designed to elicit immune responses, ideally mediated by neutralizing antibodies (NAbs), against the trimeric SARS-CoV-2 spike (S) protein. The S protein is a class I fusion protein that facilitates binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell surface, which triggers fusion between the virus and cell membrane110,148,149. Prior to contact with the host cell, the S protein is in a metastable pre-fusion conformation and the trimer undergoes substantial rearrangement at the time of virus–cell fusion150,151. Some COVID-19 vaccines include mutations that stabilize the S protein in this pre-fusion form, on the basis that this is the expected conformation prior to epithelial cell attachment, and thus immune responses directed against the pre-fusion S protein are more likely to be protective and reduce transmission. However, vaccines without this stabilization (for example, ChAdOx1 nCoV-19) have proven efficacy and so the importance of this for COVID-19 vaccines is uncertain. The S protein consists of an amino-terminal S1 subunit and a carboxy-terminal S2 subunit.