Extended interval BNT162b2 vaccination enhances peak antibody generation

Abstract

The BNT162b2 vaccine is highly effective against COVID-19 infection and was delivered with a 3-week time interval in registration studies¹. However, many countries extended this interval to accelerate population coverage with a single vaccine. It is not known how immune responses are influenced by delaying the second dose. We provide the assessment of immune responses in the first 14 weeks after standard or extended-interval BNT162b2 vaccination and show that delaying the second dose strongly boosts the peak antibody response by 3.5-fold in older people. This enhanced antibody response may offer a longer period of clinical protection and delay the need for booster vaccination. In contrast, peak cellular-specific responses were the strongest in those vaccinated on a standard 3-week vaccine interval. As such, the timing of the second dose has a marked influence on the kinetics and magnitude of the adaptive immune response after mRNA vaccination in older people.

Fig. 1. Infographic to show vaccination timings and blood collection.

Blood samples were obtained on all participants at 5–6 weeks (2–3 weeks post second dose of vaccine (V2) for the standard interval cohort and 5–6 weeks post first dose of vaccine (V1) in the extended interval cohort). Blood samples were obtained again at 13–14 weeks post first dose of vaccine in both cohorts (coinciding, 10–11 weeks post second vaccine (V2) in the standard-interval cohort and 2–3 weeks post the second dose of vaccine (V2) in the extended-interval cohort). Numbers of study participants shown represent the analysis cohort following exclusion of participants with previous natural infection.

Fig. 2. An extended interval to the second vaccination of BNT162b2 stimulates stronger spike-specific antibody responses.

a Dot plot to compare spike-specific antibody responses by Roche platform in participants who obtained the BNT162b2 vaccine with a standard interval of 3 weeks apart at bleed timepoint 1 (2–3 weeks post vaccine dose 2) and timepoint 2 (10–11 weeks post vaccine dose 2) (Wilcoxon matched-pair signed-rank test, p < 0.0001). b Dot plot to compare spike-specific antibody responses by Roche platform in participants who obtained the BNT162b2 vaccine with an extended interval at bleed timepoint 1 (5–6 weeks post vaccine dose 1) and bleed timepoint 2 (2–3 weeks post vaccine dose 2) (Wilcoxon matched-pair signed-rank test, p < 0.0001). c The kinetics of the anti-spike antibody of the 2 different vaccine schedules are shown over a 14-week period. Those participants who obtained the BNT162b2 vaccine with a standard 3-week interval are shown in blue, while those who received an extended interval to second-dose vaccination of BNT162b2 are shown in red (SEM is shown). d Dot plot to compare spike-specific antibody responses by Roche platform in the participants 2–3 weeks after the second dose of BNT162b2 vaccination in the standard- and extended-interval cohorts (median and IQR shown) (Mann–Whitney U test, p < 0.0001).

Fig. 3. Standard-interval vaccination with BNT162b stimulates a greater peak cellular response.

a Dot plot to compare spike-specific cellular responses by IFN-γ ELISpot in participants who obtained the BNT162b2 vaccine with a standard interval of 3 weeks apart at bleed time point 1 (2–3 weeks post vaccine dose 2) and timepoint 2 (10–11 weeks post vaccine dose 2) (Wilcoxon matched-pairs signed rank test; p < 0.0001). b Dot plot to compare spike-specific antibody responses by IFN-γ ELISpot in participants who obtained the BNT162b2 vaccine with an extended interval at bleed timepoint 1 (5–6 weeks post vaccine dose 1) and timepoint 2 (2–3 weeks post vaccine dose 2) (Wilcoxon matched-pair signed-rank test). c The percentage of donors with a positive IFN-γ ELISpot T-cell response is shown in the two different vaccine-interval cohorts over a 14-week period. The percentage response of those donors receiving the vaccine doses on a standard interval are shown in blue, while those receiving it on an extended interval are shown in red. d Dot plot to compare spike-specific cellular responses by ELISpot in the participants 2–3 weeks after the second dose of BNT162b2 vaccination in the standard- and extended-interval cohorts (median and IQR shown) (Mann–Whitney U test, p < 0.0001).