SARS-CoV-2 Glycosylation Suggests That Vaccines Should Have Adopted the S1 Subunit as Antigen.

Extant SARS-CoV-2 vaccines use the trimeric spike (S) protein as antigen. In the virus, the spike region is extensively glycosylated, modulating immune surveillance. Because they have been defused, many epitopes in the vaccine sidetrack the immune response. Only the receptor binding domain within the S1 subunit is well-exposed to antibody recognition. After proteolytic virus activation, the S1 subunit offers additional epitopes with antibody exposure. Thus, vaccines adopting the S1 subunit as antigen would have been more efficacious than the existing ones.