Convergent neutralizing antibodies to SARS-CoV-2 variants over 2.5 years after BA.5/BF.7 breakthrough infection

Objectives To investigate the long-term evolution of neutralizing antibody responses after BA.5/BF.7 breakthrough infection (BTI) in previously vaccinated individuals. Methods We conducted a 2.5-year longitudinal study of 29 individuals who experienced BA.5/BF.7 BTI in late 2022 in China. Neutralizing antibody titers against D614G and Omicron subvariants (BA.5, XBB.1.5, EG.5.1, KP.2, KP.3, XEC, and LB.1) were measured prior to BTI, at approximately three weeks post-BTI, and at serial timepoints over the subsequent two years. Results Before BTI, individuals had limited neutralization titers to D614G and undetectable titers against Omicron subvariants. Approximately three weeks after BTI, neutralizing titers against D614G and BA.5 increased significantly, whereas titers to XBB.1.5, EG.5.1, KP.2, KP.3, XEC, and LB.1 increased but remained low. Over the following two years, the neutralizing titers to D614G and BA.5 gradually declined, whereas cross-reactive titers against Omicron subvariants increased progressively. By 2.5 years post-BTI, neutralizing titers against all tested variants had almost reached comparable levels. Conclusions Long-term neutralizing antibody response after BA.5/BF.7 BTI is characterized by gradual broadening of cross-neutralization, and convergent antibody titers against Omicron subvariants, possibly driven by repeated infections. These findings provide crucial insights into long-term antibody response after repeated antigen exposure and inform the design of vaccination strategies.