Accurate evaluation of live-virus microneutralisation for SARS-CoV-2 variant JN.1 in the assessment of vaccination and therapeutics
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Giulia Dowgier Agnieszka Hobbs David Greenwood Marianne Shawe-Taylor Phoebe Stevenson-Leggett James Bazire Becky Penn Ruth Harvey Legacy Investigators Crick COVID serology pipeline Vincenzo Libri George Kassiotis Steve Gamblin Nicola Lewis Bryan Williams Charles Swanton Sonia Gandhi David LV Bauer Edward Carr Emma Wall Mary WuAbstract
Emerging SARS-CoV-2 variants require rapid assessments of pathogenicity and evasion of existing immunity to inform policy. A crucial component of these assessments is accurate estimation of serum neutralising antibody titres using cultured live virus isolates. Here, we report a comparison of culture methods for Omicron sub-variant JN.1 and the subsequent evaluation of neutralising antibody titres (nAbTs) in recipients of BNT162b2-XBB.1.5 monovalent and the ancestral/BA.4/5 containing bivalent vaccines. We compared culture of JN.1 in either Vero V1 cells or Caco-2 cells, finding culture in Vero V1 either resulted in low-titre stocks or induced crucial mutations at the Spike furin cleavage site (FCS). Using sequence-clean culture stocks generated in Caco-2 cells, we assessed serum samples from 71 healthy adults eligible for a COVID-19 vaccination given as a 5th dose booster in the UK: all participants had detectable nAbs against JN.1 prior to vaccination, with baseline/pre-existing nAbTs between both vaccine groups comparable (p = 0.240). However, nAbTs against JN.1 post-vaccination were 2.6-fold higher for recipients of the monovalent XBB.1.5 vaccine than the BA.4/5 bivalent vaccine (p < 0.001). Further, at clinically relevant concentrations the therapeutic monoclonal antibody Sotrovimab marginally maintains neutralisation of JN.1. Regular re-appraisal of methods and policy outcomes as new variants arise is required to ensure robust data are used to underpin future severity assessments and vaccine strain selection decisions.
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10.1016/j.vaccine.2025.126960
Europe PubMed Central
40056806
Pubmed
40056806
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