Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA. 2.12. 1, BA. 4 and BA. 5 exhibit higher transmissibility than the BA. 2 lineage 1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA. 2.12. 1, BA. 4 and BA. 5 (BA. 4 and BA. 5 are hereafter referred collectively to as BA. 4/BA. 5) exhibit similar binding affinities to BA. 2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA. 2.12. 1 and BA. 4/BA. 5 display increased evasion of neutralizing antibodies compared with BA. 2 against plasma from triple-vaccinated individuals or from individuals who developed a BA. 1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles 2, epitope distribution 3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA. 1 infection. BA. 1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA. 1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA. 1 infection can also induce new clones of BA. 1-specific antibodies that potently neutralize BA. 1. Nevertheless, these neutralizing antibodies are largely evaded by BA. 2 and BA. 4/BA. 5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab 4 and cilgavimab 5 can effectively neutralize BA. 2.12. 1 and BA. 4/BA. 5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA. 1 infection, suggesting that BA. 1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.