Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- and infection-induced immunity. We examine the sensitivity of these sub-lineages and other major variants to neutralizing antibodies from mRNA-vaccinated and boosted individuals, as well as recovered COVID-19 patients, including those infected with Omicron. We find that all Omicron sub-lineages, especially BA.1 and BA.1.1, exhibit substantial immune escape that is largely overcome by mRNA vaccine booster doses. While Omicron BA.1.1 escapes almost completely from neutralization by early-pandemic COVID-19 patient sera and to a lesser extent from sera of Delta-infected patients, BA.1.1 is sensitive to Omicron-infected patient sera. Critically, all Omicron sub-lineages, including BA.2, are comparably neutralized by Omicron patient sera. These results highlight the importance of booster vaccine doses for protection against all Omicron variants and provide insight into the immunity from natural infection against Omicron sub-lineages. Display omitted •BA.1.1, BA.1, and BA.2 escape neutralization by two-dose mRNA vaccinee sera•Booster vaccination recovers Omicron immunity to levels comparable to Delta•Sera from Omicron, but not D614G or Delta, COVID-19 patients neutralize Omicron•The Omicron “EPE214” insertion does not dictate neutralization resistance The emerging SARS-CoV-2 Omicron variants may threaten existing COVID-19 immunity. Evans and colleagues examine immunity against the BA.1.1 and BA.2 variants, as well as prior SARS-CoV-2 variants, in two- and three-dose vaccinated individuals and recovered COVID-19 patients. Booster vaccination, but not two-dose vaccinee or non-Omicron-infected patient sera, neutralizes Omicron.