Booster vaccination with messenger RNA (mRNA) vaccines has been offered to adults in England starting on 14 September 2021. We used a test-negative case–control design to estimate the relative effectiveness of a booster dose of BNT162b2 (Pfizer-BioNTech) compared to only a two-dose primary course (at least 175 days after the second dose) or unvaccinated individuals from 13 September 2021 to 5 December 2021, when Delta variant was dominant in circulation. Outcomes were symptomatic coronavirus disease 2019 (COVID-19) and hospitalization. The relative effectiveness against symptomatic disease 14–34 days after a BNT162b2 or mRNA-1273 (Moderna) booster after a ChAdOx1-S (AstraZeneca) and BNT162b2 as a primary course ranged from around 85% to 95%. Absolute vaccine effectiveness ranged from 94% to 97% and was similar in all age groups. Limited waning was seen 10 or more weeks after the booster. Against hospitalization or death, absolute effectiveness of a BNT162b2 booster ranged from around 97% to 99% in all age groups irrespective of the primary course, with no evidence of waning up to 10 weeks. This study provides real-world evidence of substantially increased protection from the booster vaccine dose against mild and severe disease irrespective of the primary course.
Real-world effectiveness data has demonstrated high levels of short-term protection by COVID-19 vaccines against clinical disease and, more so, against severe outcomes, including hospitalization and death1,2,3,4,5,6,7. Nevertheless, there is evidence that protection against symptomatic disease wanes over time8,9. Booster doses have now been implemented in the United Kingdom and elsewhere in order to combat the rise in COVID-19 cases and the additional threat of the winter 2021 influenza season.
We recently reported that vaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% confidence interval (CI), 45–49.6) and 69.7 (95% CI, 68.7–70.5) by ≥20 weeks against the Delta variant for ChAdOx1-S (AstraZeneca) and BNT162b (Pfizer-BioNTech)), respectively. Vaccine effectiveness against severe disease outcomes remained high up to 20 weeks after vaccination in most groups; nevertheless, greater waning was seen in older adults and those with underlying medical conditions compared to young, healthy adults8.
In the United Kingdom, COVID-19 booster vaccines were introduced on 14 September 2021. Using evidence from the COV-BOOST trial, which demonstrated that the mRNA vaccines provide a strong booster effect with low reactogenicity, regardless of the vaccine given in the primary course, the UK Joint Committee on Vaccination and Immunisation recommended either a BNT162b2 or a half dose (50 µg) of mRNA-1273 (Moderna) vaccine to be given as a booster dose no earlier than 6 months after completion of the primary vaccine course10,11. In this initial phase of the UK booster program, the following groups were eligible: all adults >50 years and those 16–49 years with underlying health conditions that put them at higher risk of severe COVID-19, adult carers and adult household contacts (aged ≥16 years) of immunosuppressed individuals and healthcare workers.
In this study, we aimed to estimate the effectiveness of the BNT162b2 and mRNA-1273 booster vaccines against symptomatic disease, hospitalization and death in adults in England. Table 1 outlines the main findings and implications for policy of our study.
Descriptive statistics and characteristics
From 13 September 2021 to 5 December 2021, there were a total of 893,845 eligible test results for individuals aged ≥18 years with a test date within 10 days of their symptom onset date and a link to the National Immunisation Management System (NIMS), with a 91.04% match rate. Of these eligible participants, 278,096 (31.1%) were unvaccinated, 223,198 received ChAdOx1-S 175 days after a second dose and 171,079 received BNT162b2 175 days after a second dose. Of those who had received a booster dose, 89,019 received a ChAdOx1-S primary course and 132,453 received a BNT162b2 primary course. Of the 343,955 positive cases included in the analysis, 4,377 (1.27%) were hospitalized for any reason (excluding injuries) within 14 days of the test. A description of the eligible tests is given in Supplementary Table 1.
Vaccine effectiveness for symptomatic disease
An overall effect on the proportion of cases and controls was seen from around day 7 after the booster dose and stabilized at day 11 (Extended Data Fig. 1). In individuals aged 18 to 49 years where the primary course was ChAdOx1-S vaccine, relative to those who had received only two doses, effectiveness against symptomatic disease peaked at 14–35 days after the BNT162b2 booster at 89.6% (95% CI, 88.6–90.4) and 95.3% (95% CI, 91.8–97.3) after the mRNA-1273 booster (Table 2 and Fig. 1). In individuals where BNT162b2 was the primary course, relative vaccine effectiveness 14-34 days a BNT162b2 booster was 82.8% (81.8-83.7) and after a mRNA-1273 booster 90.9% (84.5–94.7). Relative vaccine effectiveness with the BNT162b2 booster decreased slightly in the 35- to 69-day and ≥70-day periods (later follow-up was not available for mRNA-1273). The same analysis in individuals aged 50 years and older gave similar results (Table 2 and Fig. 1).
In the secondary analysis, which used the 2- to 6-day period after the booster dose as the baseline, results were similar to the primary analysis (Table 2 and Extended Data Fig. 2). In the analysis using the unvaccinated individuals as the baseline, the booster dose was associated with an absolute vaccine effectiveness from 14 to 34 days after a BNT162b2 booster of 94.4% (95% CI, 94.1–94.7) following either a ChAdOx1-S or BNT162b2 primary course in individuals 50 years and older. With an mRNA-1273 booster, absolute vaccine effectiveness was 97.0 (95% CI, 96.0–97.8) after a ChAdOx1-S primary course and 94.8% (95% CI, 92.7–96.3) after a BNT162b2 primary course (Table 3 and Extended Data Fig. 3).
Vaccine effectiveness for hospitalization and death
High levels of protection were also seen against hospitalization in both age groups. In individuals aged 50 years and older, the vaccine effectiveness 14-34 days after a BNT162b2 booster dose, relative to unvaccinated individuals, was 99.2% (95% CI, 98.6–99.5) when the primary course was ChAdOx1-S and 98.6% (95% CI, 98.0–99.0) when BNT162b2 was used as the primary course.
A similarly high level of protection was seen in the younger age group, with a vaccine effectiveness estimate of 97.5% (95% CI, 93.3–99.1) when the primary course was ChAdOx1-S and 98.8% (95% CI, 97.2–99.5) when BNT162b2 was used as the primary course (Table 3 and Fig. 2). There was little evidence of any waning in vaccine effectiveness against hospitalization up to 69 days after the booster.
Vaccine effectiveness against death in individuals 50 years and older 14–34 days after a BNT162b2 booster dose relative to the unvaccinated was 97.8 (95% CI, 94.4–99.1) after a ChAdOx1-S primary course and 98.7% (95% CI, 97.4–99.4) when the primary course was BNT162b2 (Table 4 and Fig. 2)
Interval between dose 2 and the booster dose
After assessing the distribution of intervals between dose 2 and the booster dose for cases and controls by age group and manufacturer, the interval between dose 2 and the booster was split into three periods: 25–29, 30–34 and 35 or more weeks (Extended Data Fig. 4). Due to the roll out of the vaccine program, there were more individuals who had received a second dose of BNT162b2 at an earlier time point; therefore, the majority of the individuals who had the longest interval between dose 2 and the booster had a BNT162b2 primary course. Analyses by interval between dose 2 and dose 3 were thus restricted to those who received BNT162b2 as the primary course.
A shorter interval between dose 2 and the booster of 25–29 weeks compared to the baseline interval of 35 weeks or more was associated with an increased adjusted odds ratio of 1.54 (95% CI, 1.35–1.76) for becoming a symptomatic case. This was also seen in the 30- to 34-week interval, with an adjusted odds ratio of 1.32 (1.12–1.56). Although remaining high, the adjusted vaccine effectiveness estimates decreased from 95.6% (95% CI, 94.9–96.1) in the 35 weeks or more interval to 93.2% (95% CI, 92.8–93.6) in the shortest interval between dose 2 and the booster (Supplementary Table 2). A test for the interaction effect of age was not significant (P = 0.15).
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