Estimating neutralising antibody responses against emerging SARS-CoV-2 variants utilising convalescent sera before the roll-out of XBB-lineage vaccines

Background: SARS-CoV-2 immune escape variants can alter existing vaccine effectiveness. In September 2023, we aimed to predict the neutralising response against BA.2.86 offered by XBB-lineage vaccines before vaccine roll-out utilising XBB.1.5 convalescent sera. We then assessed the response to XBB-lineage boosters from different individuals in the same cohort. Methods: A total of 78 sera samples (pre/post-XBB.1.5 infection and pre/post-XBB-lineage vaccination) were tested for live microneutralisation against SARS-CoV-2 Victoria and Omicron subvariants. Geometric means (GM) of neutralising antibody titres (nAbT) pre- and post-infection/vaccination were compared. Results: After XBB.1.5 infection, a 4-fold increase in neutralising antibody titres against BA.2.86 was observed compared to pre-infection titres (GM 51 vs 210, p ≤ 0.0001). A similar increase in BA.2.86 nAbT was seen post-XBB-lineage vaccination (GM 144 vs 600, fold change = 4.17, p ≤ 0.0001). Conclusion: XBB.1.5 infection was a suitable proxy to predict the neutralisation response following XBB-lineage vaccination. Our findings may support future vaccine development and vaccination strategies.