The UK's strategy to extend the interval between coronavirus vaccines may be paying off.
One of three approved jabs, the Pfizer-BioNTech vaccine was signed off after a study demonstrated it is 95% effective at warding off severe disease when the two doses are administered three weeks apart.
To maximise the number of people being vaccinated with a first dose, the interval was extended to up to 12 weeks, with many experts optimistic this could lead to a more potent immune response.
Scientists from the University of Birmingham have now reported the level of infection-fighting antibodies was 3.5 times higher in people over 80 who had two Pfizer-BioNTech vaccines 12 weeks apart, compared to those immunised with a three-week interval.
Older people are known to be more at risk of coronavirus complications, as well as generally having a more muted immune response post-vaccination.
Although younger people were not included in the study, the scientists expect similar results will occur in all age groups.
The preliminary results have not yet been published in a peer-reviewed journal.
"[Coronavirus] vaccines have been remarkably effective in providing large-scale protection against infection and symptomatic disease, but many questions remain regarding their optimal delivery," said study author Dr Helen Parry.
"Our study demonstrates 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."
The Birmingham scientists, in collaboration with Public Health England (PHE), analysed 172 people over 80 years old who were living independently.
Other potential participants were excluded if they showed signs of having overcome the coronavirus naturally. A previous infection has been shown to have a "major impact on the immune response to vaccination".
Of the 172 participants, 99 were given the Pfizer-BioNTech vaccine three weeks apart, while the remaining 73 waited 12 weeks for their second dose.
In the three-week group, blood samples were taken around 2.5 and 10.5 weeks after the second vaccine.
For those with the 12-week dosing interval, the first blood sample was drawn 5.5 weeks after their first jab and 2.5 weeks after the second vaccine.
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Antibodies were detected in all the participants after their second vaccine, however, levels were up to 3.5 times higher in the 12-week group.
The scientists also analysed the participants' T cells. So-called helper T-cells stimulate antibody production and assist in the development of killer T-cells, which directly destroy body cells that have already been infected by a pathogen.
T-cells also send out messages instructing the rest of the immune system to ramp up its response.
In the three-week group, three in five (60%) had "a confirmed" T-cell response two to three weeks after their second vaccine, falling to 15% eight to nine weeks later.
Only 8% in the 12-week group were found to have T-cells five to six weeks after their first jab, rising to 31% two to three weeks after the second vaccine.
Further research is required to uncover why these variations in T-cell responses occur, stressed the scientists.
Overall, the scientists have concluded extending the Pfizer-BioNTech vaccine's dosing schedule could give older people greater protection against COVID-19, the disease caused by the coronavirus.
"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," said co-author Professor Paul Moss.
"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."
Dr Gayatri Amirthalingam agreed, adding: "The higher antibody responses in people receiving two doses of the Pfizer vaccine using an extended 12-week interval provides further supportive evidence of the benefits of the UK approach to prioritise the first dose of vaccine.
"It is vital you take up the offer of vaccination as it is the best way to protect yourself and your community and to help us out of the pandemic."
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Delaying a second vaccine in a two-dose schedule is thought to better prime the immune system against an infection.
"With the human papillomavirus (HPV) vaccine, for example, the guidance says if the second dose is given before six months after the first dose, it is unlikely to generate good-enough immunity and it should be repeated no less than six months after the first dose," said Dr Peter English, former editor of Vaccines in Practice magazine.
When the Pfizer-BioNTech vaccine was being tested pre-approval, "we did not know how effective a single dose would be (it's much better than expected) and we needed to get the most vulnerable in society protected as soon as possible".
"The trade-off was it [the three-week gap] was likely to induce poorer immunity than a longer interval, increasing the likely need for additional boosters," said Dr English.
"When we realised, from the phase III trials, how effective a single dose [of the Pfizer-BioNTech jab] was going to be, it meant we could extend the interval, thereby allowing more people to get the protection from a single dose more quickly."