Extended interval BNT162b2 vaccination enhances peak antibody generation in older people

Abstract

Objectives: To assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. Design: Population based cohort study comparing immune responses 2 weeks after the second vaccine, with appropriate time-matched samples in participants who received standard or extended interval double vaccination. Setting: Primary care networks, Birmingham, UK. December 2020 to April 2021. Participants: 175 people aged over 80 years of age. All donors received the BNT162b2 Pfizer/BioNTech vaccination and were vaccinated with either a standard 3 week interval between doses or an extended interval schedule. Main outcome measures: Peak quantitative spike-specific antibody and cellular immune responses. Results: In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination. Cellular immune responses were 3.6-fold lower. Conclusion: Peak antibody responses after the second BNT162b2 vaccine are markedly enhanced in older people when this is delayed to 12 weeks although cellular responses are lower. Extended interval vaccination may therefore offer the potential to enhance and extend humoral immunity. Further follow up is now required to assess long term immunity and clinical protection.

Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province

“…In our sample, no differences in the effectiveness of BNT162b2 or mRNA-1273 vaccines emerged among those who received a delayed second dose (n = 691), as compared to people vaccinated according the standard regimen [19]. These findings are in line with a preliminary, UK-based pre-print analysis on 172 elderly subjects immunized with the BNT162b2 vaccine [35], in which the antibody response was 3.5-fold higher with a delayed interval vaccination, as compared to the standard, 3-week schedule. Although based upon limited data, thus requiring confirmation, these findings support the current Italian policy on a delayed second dose administration and might be crucial to maximize vaccination benefits in the contest of limited supplies.…”

The origins and potential future of SARS-CoV-2 variants of concern in the evolving COVID-19 pandemic

“…Another important factor to consider when determining the dosing regime comes from recent studies showing that delaying the second dose enhances immunity, with elevated antibody levels following a longer dosing interval (12 weeks) than a shorter interval (<6 weeks) for both the Pfizer 68 and the AstraZeneca 69 vaccines. Delayed second doses might thus increase the selective advantage of partial escape mutations over the short term but reduce it over the longer term given the more robust immune responses observed with a delayed booster 68,69 . Reopening As we move to reopen societies, rebuild economies, and resume social activities, contact rates will increase.…”

Comparison between one and two dose SARS-CoV-2 vaccine prioritization for a fixed number of vaccine doses

“…In the context of UK vaccination policy, the key question was around the delay between the first and second dose, with a longer delay allowing more individuals to be given some level of protection in the short term. For the Oxford/AstraZeneca vaccine, there is also compelling evidence that a delay of 12 weeks or more provides greater second dose vaccine efficacy [5], strengthening the case for an early prioritization of first doses; this has since been enhanced by studies of the Pfizer vaccine suggesting a longer delay may again offer better protection [17].…”

“…Throughout, we explored the sensitivity to the relative efficacy of the first vaccine dose (compared to the efficacy attained following two vaccine doses). We acknowledge that this is a simplified representation of a complex dynamic process, whereby new supplies of vaccine are being manufactured and distributed over time, where second dose efficacy may change depending on the inter-dose separation [5,17] and where there can be an intrinsic feedback between vaccination and population-level incidence. Nevertheless, parsimonious model structures (such as the one used in this study) may be swiftly developed and applied, whereas models with additional complexities typically require longer development times, finer-resolution data to be reliably parameterized and can result in parameter inference becoming more computationally intensive [18].…”