Two studies in Nature and Cell look at the ability of vaccine-induced and infection-induced sera to neutralize the newer BA.2.12.1, BA.4 and BA.5 sublineages of SARS-CoV-2 Omicron compared with BA.1 and BA.2. Tuekprakhon et al. and Cao et al. show that serum from triple-vaccinated individuals (Pfizer, AstraZeneca or CoronaVac), and from vaccinated individuals who experienced a breakthrough infection with BA.1, has reduced ability to neutralize BA.4/5 and BA.2.12.1 compared with BA.1/2 as a result of L452R and F486V (BA.4/5) and L452Q (BA.2.12.1) mutations in the receptor binding domain (RBD). Similar results were reported for most commercially available monoclonal antibodies in terms of further reduced neutralization activity against the newer Omicron sublineages. Tuekprakhon et al. also report that the RBD of BA.4/5 has higher affinity for the host receptor ACE2 than BA.1/2, whereas Cao et al. find that the ACE2-binding affinities are similar.