Real-world data on immune responses following heterologous prime-boost COVID-19 vaccination schedule with Pfizer and AstraZeneca vaccines in England.

BACKGROUND: There are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended ≥12-week interval between doses. METHODS: SARS-CoV-2 infection-naïve and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT. RESULTS: During March-October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously-uninfected adults, S-antibody GMC at 30 days post-second dose were lowest for ChAd-ChAd (862 [95% CI, 694 - 1069]) and significantly higher for ChAd-BNT (6233 [5522-7035]; GMR 6.29; [5.04-7.85]; p<0.001), BNT-ChAd (4776 [4066-5610]; GMR 4.55 [3.56-5.81]; p<0.001) and BNT-BNT (5377 [4596-6289]; GMR 5.66 [4.49-7.15]; p<0.001). By 12 weeks after dose two, S-antibody GMC had declined in all groups and remained significantly lower for ChAd-ChAd compared to ChAd-BNT (GMR 5.12 [3.79-6.92]; p<0.001), BNT-ChAd (GMR 4.1 [2.96-5.69]; p<0.001) and BNT-BNT (GMR 6.06 [4.32-8.50]; p<0.001). Previously infected adults had higher S-antibody GMC compared to infection-naïve adults at all time-points and with all vaccine schedules. CONCLUSIONS: These real-world findings demonstrate heterologous schedules with adenoviral-vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.

Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021.

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2-4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2-4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.

Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England.

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50-89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14-35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65-84 days) compared with those vaccinated with a standard (19-29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14-35 days post dose 2 for BNT162b2 than AZD1222. 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 dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.