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

ABSTRACT

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-naive 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-naive 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.