Impact of LP.8.1-Adapted mRNA Vaccination on SARS-CoV-2 Variant Neutralisation
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SARS-CoV-2 continues to evolve, with successive variants evading immunity established through prior infection or vaccination. By mid-2025, the XFG lineage emerged and began replacing LP.8.1 across multiple geographical regions, indicating further adaptive evolution within the JN.1-derived clade. We therefore assessed immune responses in 42 healthcare workers who received 30 μg of LP.8.1-adapted mRNA vaccine (Comirnaty LP.8.1, BioNTech–Pfizer, Mainz, Germany) in September 2025. Post LP.8.1 vaccination, anti-spike IgG and anti-spike omicron IgG changed 2·2-fold and 1·9-fold, respectively, revealing significant increases. Neutralising antibody responses against pseudovirus particles (pp) with spike proteins of various SARS-CoV-2 variants revealed a significant increase in neutralisation of JN.1pp (mean change 4·2-fold), LP.8.1pp (8·2-fold), NB.1.8.1pp (8·6-fold), XFGpp (16·5-fold), and BA.3.2.2pp (2·2-fold). Fold increase in GMT neutralisation post-vaccination was highest for XFGpp whilst absolute post-vaccination neutralisation GMT was lowest for BA.3.2.2pp. Our data suggest that the LP.8.1 mRNA vaccination most likely increases protection against severe disease courses and sequelae of COVID-19 caused by the currently circulating XFG variant. Strengthening humoral immunity against BA.3.2 variants may require further vaccine refinement.
