Comparative C1q- and FcγR-binding antibody profiles and immunoglobulin type signatures after Omicron XBB-adapted PHH-1V81 and BNT162b2 COVID-19 boosters

Immune-evasive SARS-CoV-2 variants have spurred Omicron-adapted boosters. PHH-1V81 is an adjuvanted Omicron XBB.1.16 receptor-binding domain (RBD) protein vaccine. In mRNA-primed adults (primary series and ≥ 1 vaccination booster; ~50% with prior-infection serological evidence), we characterised IgA, IgG1-4, and C1q-/FcγR-binding antibodies to vaccine-target and ancestral WH1 antigens at day 14 (D14) and at 3 months (M3) after PHH-1V81 versus BNT162b2 XBB.1.5 boosting. Compared to homologous boosting, PHH-1V81 induced higher, more durable RBD-specific IgA titres through M3, alongside stronger RBD-specific IgG1-4 and C1q/FcγR-binding antibody responses. BNT162b2 increased spike (S)-specific IgG, particularly IgG3, and S-directed C1q-/FcγR-binding antibodies. Both boosters elicited a shift from FcγR-engaging cytophilic IgG1/IgG3 subclasses towards non-cytophilic IgG2/IgG4 responses post-D14. PHH-1V81 sustained Omicron cross-recognition, reducing ancestral variant immune imprinting, and predicted lower breakthrough risk via IgG1, XBB neutralisation and C1q, with FcγR similarly protective. Overall, PHH-1V81 induced a robust RBD-centred protective functional antibody profile in contrast to BNT162b2 XBB.1.5.