Abstract
BackgroundThere are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended ≥12-week interval between doses. MethodsSARS-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. ResultsDuring 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. ConclusionsThese 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.
Highlights
COVID-19 vaccines are highly effective in preventing severe disease and deaths due to SARS-CoV-2
During March – October 2021, 75,827 individuals were identified in National Immunisation Management System (NIMS) as receiving heterologous vaccination, 9489 were invited to participate by completing the online survey, 1836 responses were received and 656 met the eligibility criteria and were recruited for the evaluation (Fig. 1) amongst ChAd-BNT recipients, sufficient serum within the specified time frame was available for 216 participants at day 30 and 195 at week 12 after the second vaccine dose
A heterologous schedule provides higher antibody levels than ChAd-ChAd, with higher antibody responses after ChAd-BNT compared to BNT-ChAd
Summary
COVID-19 vaccines are highly effective in preventing severe disease and deaths due to SARS-CoV-2. Pre-licensure clinical trial data demonstrated high humoral and cellular responses after a two-dose schedule with high vaccine effectiveness against symptomatic disease.[2,3] The UK, like most other countries, recommended immunisation with the same vaccine brand for both doses where possible, a heterologous prime-boost vaccine schedule was advised for a small number of individuals in specific circumstances, such as serious adverse events after the first dose, including anaphylaxis.[4] Following rare reports of vaccine-induced thrombocytosis and thrombocytopenia (VITT) after the first dose of ChAd, many countries recommended completing the schedule with an mRNA vaccine for younger adults who had received an adenoviral vector vaccine for their primary dose.[5]. 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. 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
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