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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22271126

ABSTRACT

In contrast to the increasing levels of high avidity S antibody measured by the Roche assay in the first 6 months following natural infection, marked waning is seen post 2 or 3 doses of vaccine. Although the kinetics differ between those with vaccine-induced immunity compared to those infected prior to vaccination (hybrid immunity), waning rates appear to be similar following 2 or 3 doses of vaccine. These data should allow countries to optimise the timing of future doses of vaccine.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-21266692

ABSTRACT

IntroductionThere are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca). MethodsA prospective, cohort study to assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving either (i) two BNT162b2 doses <30 days apart (BNT162b2-control), (ii) two BNT162b2 doses [≥]30 days apart (BNT162b2-extended) or (iii) two AZD1222 doses [≥]30 days apart (AZD1222-extended) in London, England. SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster were compared. ResultsOf 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208; 95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560; n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421; n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704; n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants. ConclusionsWe observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21261140

ABSTRACT

IntroductionIn January 2021, the UK decided to prioritise the delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval until the second dose up to 12 weeks. MethodsSerological responses were compared after BNT162b2 and AZD1222 vaccination with varying intervals in uninfected and previously-infected adults aged 50-89 years. These findings are evaluated against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. ResultsWe recruited 750 participants aged 50-89 years, including 126 (16.8%) with evidence of previous infection; 421 received BNT162b2 and 329 and AZD1222. For both vaccines, over 95% had seroconverted 35-55 days after dose one, and 100% seroconverted 7+ days after dose 2. Following a 65-84 day interval between two doses, geometric mean titres (GMTs) at 14-34 days were 6-fold higher for BNT162b2 (6703; 95%CI, 5887-7633) than AZD1222 (1093; 806-1483), which in turn were higher than those receiving BNT162b2 19-29 days apart (694; 540 - 893). For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with interval between doses. Higher two-dose VE was observed with >6 week intervals between BNT162b2 doses compared to the authorised 3-week schedule, including [≥]80 year-olds. ConclusionOur findings support the UK approach of prioritising the first dose of COVID-19 vaccines, with evidence of higher protection following extended schedules. Given global vaccine constraints, these results are relevant to policymakers, especially with highly transmissible variants and rising incidence in many countries. FundingPublic Health England

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