Anti-spike antibody trajectories in individuals previously immunised with BNT162b2 or ChAdOx1 following a BNT162b2 booster dose

<ns3:p><ns3:bold>Background: </ns3:bold>The two most common SARS-CoV-2 vaccines in the UK, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca), employ different immunogenic mechanisms. Compared to BNT162b2, two-dose immunisation with ChAdOx1 induces substantially lower peak anti-spike antibody (anti-S) levels and is associated with a higher risk of breakthrough infections. To provide preliminary indication of how a third booster BNT162b2 dose impacts anti-S levels, we performed a cross-sectional analysis using capillary blood samples from vaccinated adults participating in Virus Watch, a prospective community cohort study in England and Wales.</ns3:p><ns3:p> <ns3:bold>Methods: </ns3:bold>Blood samples were analysed using Roche Elecsys Anti-SARS-CoV-2 S immunoassay. We analysed anti-S levels by week since the third dose for vaccines administered on or after 1 September 2021 and stratified the results by second-dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability.</ns3:p><ns3:p> <ns3:bold>Results: </ns3:bold>Anti-S levels peaked at two weeks post-booster for BNT162b2 (22,185 U/mL; 95%CI: 21,406-22,990) and ChAdOx1 second-dose recipients (19,203 U/mL; 95%CI: 18,094-20,377). These were higher than the corresponding peak antibody levels post-second dose for BNT162b2 (12,386 U/mL; 95%CI: 9,801-15,653, week 2) and ChAdOx1 (1,192 U/mL; 95%CI: 818-1735, week 3).  No differences emerged by second dose vaccine type, age, sex or clinical vulnerability. Anti-S levels declined post-booster for BNT162b2 (half-life=44 days) and ChAdOx1 second dose recipients (half-life=40 days). These rates of decline were steeper than those post-second dose for BNT162b2 (half-life=54 days) and ChAdOx1 (half-life=80 days).</ns3:p><ns3:p> <ns3:bold>Conclusions: </ns3:bold>Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but levels are projected to be similar after six months for BNT162b2 recipients. Higher peak anti-S levels post-booster may partially explain the increased effectiveness of booster vaccination compared to two-dose vaccination against symptomatic infection with the Omicron variant. Faster waning trajectories post-third dose may have implications for the timing of future booster campaigns or four-dose vaccination regimens for the clinically vulnerable.</ns3:p>