Nature Immunology, Published online: 30 November 2021; doi:10.1038/s41590-021-01088-9

Lanz and colleagues show that the first dose of the BNT162b2 mRNA vaccine against SARS-CoV-2 activates a non-neutralizing recall response predominantly targeting the S2 subunit of the spike protein, while the second dose boosts neutralizing antibodies specific for the receptor binding domain of the spike protein.