Extended interval BNT162b2 vaccination enhances peak antibody generation in older people

ObjectivesTo assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. DesignPopulation 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. SettingPrimary care networks, Birmingham, UK. December 2020 to April 2021. Participants172 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 measuresPeak quantitative spike-specific antibody and cellular immune responses. ResultsIn 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. ConclusionPeak 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. What is already known on this topicThe BNT162b2 vaccine is highly effective against Covid-19 infection and was delivered with a 3-week time interval in registration studies. However, this interval has been extended in many countries in order to extend population coverage with a single vaccine. It is not known how immune responses after the second dose are influenced by delaying the second vaccine. What this study addsWe provide the first assessment of immune responses in the first 14 weeks after standard or extended interval BNT162b2 vaccination and show that delaying the second dose acts to strongly boost the peak antibody response in older people. The extended interval vaccination may offer a longer period of clinical protection. This information will be of value in optimizing vaccine regimens and help guide guide vaccination policies.