Abstract
Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe the potency and breadth of neutralizing and binding antibody responses against a large panel of variants following an Omicron BA.1 or BA.2 breakthrough infection in a heterogeneous cohort of individuals with diverse exposure histories. Both BA.1 and BA.2 breakthrough infections significantly boost antibody levels and broaden antibody reactivity. However, this broader immunity induced by BA.1 and BA.2 breakthrough infections does not neutralize Omicron BQ and XBB subvariants efficiently. While these subvariants are not neutralized well by post-breakthrough sera, suggesting escape, binding non-neutralizing antibody responses are sustained. In summary, our data suggest that while BA.1 and BA.2 breakthrough infections broaden the immune response to SARS-CoV-2 spike, the induced neutralizing antibody response is still outpaced by viral evolution.