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Study finds delaying second Pfizer COVID-19 vaccine dose boosts immune response

An NIHR and UKRI funded study has found that people aged over 80 who received their second dose of the Pfizer–BioNTech mRNA vaccine after 12 weeks have significantly higher peak antibody levels than those who received it after 3 weeks.

The study is the world’s first comparison of the immune response in any age group between administering the second Pfizer COVID-19 vaccine dose at three and 12 week intervals.

Data from the preprint paper show that people aged over 80 who were given the second vaccine after 12 weeks had a three-and-a-half times greater antibody response compared to those who received it at three weeks.

The researchers also found peak T-Cell immune responses were lower after the delayed 12 week second vaccine. However this did not cause antibody levels to decline more quickly over the nine weeks following the booster shot - with responses comparable when measured at a similar time point following the first dose.

The team concluded that extending administration of the second Pfizer vaccine to 12 weeks potentially enhances and extends antibody immunity, which is believed to be important in virus neutralisation and prevention of infection against COVID-19.

Methodology

175 older people over 80 took part in the study - with 99 participants receiving the second vaccine at three weeks, and a further 73 participants receiving their second dose at 12 weeks.

Participants gave blood samples for lab analysis after their first vaccine and then two to three weeks after their second dose.

Results

After their second vaccine, spike-specific antibodies were detected in all participants, irrespective of how far apart their doses were. However, after the second vaccine the average concentration of antibodies was 3.5 times higher in the 12-week interval group (4,030 U/ml) compared to the three-week interval group (1,138 U/ml).

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.

First author Dr Helen Parry, NIHR Academic Clinical Lecturer at the University of Birmingham, said:

“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 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.”

The study was supported by the UK Coronavirus Immunology Consortium and the British Society for Immunology.

Find out more:

University of Birmingham press release