Role of prior immunity in binding to spike of "future" Omicron subvariants

Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of "future" variants in the context of such heterogeneous exposure has not been studied.

We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework.

Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both 'High S' and 'Low S' of Delta and Omicron periods were closely related to "future" subvariants by Antigenic Cartography. Sera from different S groups clustered together with 'Low S' interspersed between 'High S' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies.

Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to "future" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the 'Low S' antibody demonstrates similar binding.