With B.1.617.2, infections occurring after two vaccinations had comparable peak viral burden Rabbit polyclonal to ZNF43 as those in unvaccinated individuals. BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the progressively dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is usually reduced with the B.1.617.2 variant (complete difference of 10C13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural contamination. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic contamination with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior contamination and in more youthful adults. With B.1.617.2, infections occurring after two vaccinations had comparable peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2. values were obtained using the two-sided Wald test without adjustment for multiple comparisons. Calendar time was split into two epochs when most cases detected in the survey were ORF1ab?+?N positive (B.1.1.7 compatible) and then when triple positives became dominant (B.1.617.2 compatible) (Extended Data Fig. ?Fig.1).1). Estimates from the former are similar to those from individuals aged 16 years previously published on data to 8 May 2021 but with slightly wider 95% CIs due to splitting time after the second dose at 14 d in this analysis. Observe Supplementary Table 4 for unadjusted heterogeneity values. VE post-second doses GSK2256098 changes over time from vaccination (observe Fig. ?Fig.22 and Extended Data Figs. ?Figs.44 and ?and55 for changes in individuals aged 18C64 years), so estimates in this table are an average over follow-up included in this analysis. In the B.1.617.2-dominant period, in individuals aged 18 years, there was evidence of reduced effectiveness compared to GSK2256098 the B.1.1.7-dominant period 21 d after the first ChAdOx1 GSK2256098 vaccination but not 14 d after the second (heterogeneity values were obtained GSK2256098 using the two-sided Wald test without adjustment for multiple comparisons. Observe Supplementary Table 5 for unadjusted heterogeneity values. Observe Table ?Table11 for estimates in individuals 18 years of age in both B.1.1.7-dominant and B.1.617.2-dominant periods. VE post-second doses changes over time from vaccination (Fig. ?(Fig.22 and Extended Data Figs. ?Figs.44 and ?and5),5), so estimates in this table are an average over follow-up included in this analysis. In the B.1.617.2-dominant period, VE against new PCR-positive cases of individuals aged 18C64 years was significantly lower for ChAdOx1 versus BNT162b2 21 d after one vaccination and 14 d after two vaccinations (heterogeneity values were obtained using the two-sided Wald test without adjustment for multiple comparisons. Approximately 10% of visits in the B.1.617.2-dominant period occurred in vaccinated individuals with evidence of prior SARS-CoV-2 infection (Supplementary Table 2). Protection against new PCR-positive cases was significantly higher for vaccinated individuals with prior contamination than vaccinated individuals without prior contamination for both ChAdOx1 and BNT162b2 (heterogeneity thanks the anonymous reviewers for their contribution to the peer review GSK2256098 of this work. Editor recognition statement Joao Monteiro was the primary.