Delaying second Pfizer/BioNTech vaccines to 12 weeks significantly increases antibody responses in older people

Several COVID-19 vaccines are in use in the UK, including the Pfizer/BioNTech vaccine which was the first to be rolled out to a large number of people. The Pfizer/BioNTech vaccine was originally authorised for a three-week interval between doses; however, several countries, including the UK, chose to expand this to a 12-week interval to allow more people to receive a single dose of the vaccine more quickly. It is important to understand the effect of a longer gap between doses on the immune response generated. 

This study by the University of Birmingham, funded by the UK Coronavirus Immunology Consortium and in collaboration with Public Health England, investigated this effect. It found that, in people aged 80 or older and living independently, antibody responses to SARS-CoV-2 (the virus that causes COVID-19) were 3.5 times higher following a 12-week interval, compared with a 3-week interval. This was the first study to directly compare immune responses using the 3- and 12-week intervals for this vaccine in any age group. 

This study is available as a preprint via medRxiv (a preprint is an early version of a study that still needs to be peer-reviewed). The research was jointly funded by UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR) and supported by the British Society for Immunology.

The researchers took blood samples from 175 people who were aged 80 or older and living independently, once after their first vaccine and then again 2–3 weeks after their second vaccine. In the group, 99 people had their second vaccine after three weeks, while 73 had their second vaccine at 12 weeks. 

Participants who had previous infection (10 in the three-week interval group and five in the 12-week interval group) were excluded from the analysis as previous infection has been shown to have a major impact on the immune response to vaccination.

The research found that extending the second dose interval to 12 weeks increased the peak antibody response 3.5-fold compared with those who had the second vaccine at three weeks.  

In relation to the cellular (or T cell) immune response, which plays an important role in supporting and maintaining antibody production, the team found that within the three-week interval group, 60% had a confirmed cellular response at two to three weeks following the second vaccine – although this fell to only 15% eight to nine weeks later. 

The proportion of participants showing a cellular response in the 12-week-interval group was only 8% at five to six weeks after the first vaccine, but this rose to 31% two to three weeks after the second vaccine.  Research is required to further explore these variations in responses.

The team concluded that extending administration of the second Pfizer/BioNTech vaccine to 12 weeks potentially enhances and extends antibody immunity, which is believed to be important in virus neutralisation and prevention of infection. While the Pfizer/BioNTech vaccine has been shown to be very effective at preventing more serious symptoms of COVID-19, and reducing the number of people who develop the disease, it is important to remember that it is not 100% effective.


First author Dr Helen Parry, NIHR Academic Clinical Lecturer at the University of Birmingham, said of the study: “SARS-CoV-2 vaccines have been remarkably effective in providing large-scale protection against infection and symptomatic disease – but many questions remain regarding their optimal delivery for provision of effective and sustained immunity.

“This is the first-time antibody and cellular responses have been studied when the second vaccine is given after an extended interval. Our study demonstrates that peak antibody responses after the second Pfizer/BioNTech vaccine are markedly enhanced in older people when this is delayed to 12 weeks. 

“This research is crucial, particularly in older people, as immune responses to vaccination deteriorate with age. Understanding how to optimise COVID-19 vaccine schedules and maximise immune responses within this age group is vitally important.”


Professor Paul Moss, Principal Investigator of the UK Coronavirus Immunology Consortium from the University of Birmingham, added: “The enhanced antibody responses seen after an extended interval may help to sustain immunity against COVID-19 over the longer term and further improve the clinical efficacy of this powerful vaccine platform.

“Our research findings may be important in the development of global vaccination strategy as extension of interval of the second vaccine dose in older people may potentially reduce the need for subsequent booster vaccines.

“Taking a collaborative approach to research through the UK Coronavirus Immunology Consortium and National Core Studies has allowed us to drive forward our knowledge at an incredible pace and build our understanding of how different components of the immune system respond to COVID vaccines. This knowledge will allow us to optimise vaccination protocols and maximise protection against SARS-CoV-2 within our population.”


More information on the study can be found on our Publications page.