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.
Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan
