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Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants
Ashley David Otter; Silvia D'Arcangelo; Heather Whitaker; Jacqueline Hewson; Sarah Foulkes; Ana Atti; Michelle Cole; Ezra Linley; Simon Tonge; Nipunadi Hettiarachchi; Noshin Sajedi; Davina Calbraith; Chris Norman; Elen de Lacy; Lesley Price; Sally Stewart; Lisa Cromey; Diane Corrigan; - SIREN study group; Cathy Rowe; Colin Brown; Jasmin Islam; Amanda Semper; Susan Hopkins; Victoria Hall; Tim Brooks.
  • Ashley David Otter; UK Health Security Agency
  • Silvia D'Arcangelo; UK Health Security Agency
  • Heather Whitaker; UK Health Security Agency
  • Jacqueline Hewson; UK Health Security Agency
  • Sarah Foulkes; UK Health Security Agency
  • Ana Atti; UK Health Security Agency
  • Michelle Cole; UK Health Security Agency
  • Ezra Linley; UK Health Security Agency
  • Simon Tonge; UK Health Security Agency
  • Nipunadi Hettiarachchi; UK Health Security Agency
  • Noshin Sajedi; UK Health Security Agency
  • Davina Calbraith; UK Health Security Agency
  • Chris Norman; Health and Care Research Wales
  • Elen de Lacy; Public Health Wales
  • Lesley Price; Glasgow Caledonian University and Public Health Scotland
  • Sally Stewart; Glasgow Caledonian University and Public Health Scotland
  • Lisa Cromey; Public Health Agency Northern Ireland
  • Diane Corrigan; Public Health Agency Northern Ireland
  • - SIREN study group;
  • Cathy Rowe; UK Health Security Agency
  • Colin Brown; UK Health Security Agency
  • Jasmin Islam; UK Health Security Agency
  • Amanda Semper; UK Health Security Agency
  • Susan Hopkins; UK Health Security Agency
  • Victoria Hall; UK Health Security Agency
  • Tim Brooks; UK Health Security Agency
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22274025
BackgroundUnderstanding immunological responses to SARS-CoV-2 vaccinations is integral to the management of SARS-CoV-2. We aimed to investigate determinants of antibody response to the BNT162b2 vaccine. MethodsA cross-sectional analysis of anti-spike binding antibodies in serum samples from healthcare workers after one or two doses. Post-vaccination interval was restricted to [≥]21 days after dose 1, [≥]14 days after dose 2. The primary outcome was anti-S titres with explanatory variables dose, previous infection, dosing interval, age, ethnicity, and comorbidities. Multivariable linear regression was also conducted. ResultsParticipants (n=5,871) included 3,989 post-dose 1, 1,882 post-dose 2. In SARS-CoV-2 infection naive, 99.65% seroconverted after dose 1 and >99.9% seroconverted after dose 2. Geometric mean anti-S titre in the naive cohort was 75.48 Binding Antibody Units/ml after dose 1, 7,049 BAU/ml after dose 2. Anti-S titres were higher in those with previous infection (2,111 BAU/ml post-dose 1, 16,052 BAU/ml post-dose 2), and increased with time between infection and vaccination 3 months 1,970 (1,506-2,579) vs 9 months; 13,759 (8,097-23,379). Longer dosing intervals increased antibody response post-dose 2 11-fold higher with a longer interval (>10 weeks) than those with shorter intervals, across all age-groups. Younger participants had higher mean titres (>2.2-fold higher). Multivariable regression modelling corroborated the above associations, and also found higher titres associated with being female or from an ethnic minority but lower titres among immunocompromised participants. ConclusionThe number of antigen exposures and timing between vaccinations plays a significant role in the magnitude of the post-vaccination antibody response, with implications for long-term protection and post-booster antibody responses.

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