Longer interval between Pfizer vaccine doses boosts antibody protection

© iStock/Courtney Hale

A longer dosing schedule for the Pfizer COVID-19 vaccine triggered the most effective immune response, new research has found.

A new and extensive pre-print study led by the University of Oxford found that two doses of the Pfizer vaccine, administered with a longer dosing interval, generated higher antibody levels and a higher proportion of ‘helper’ T cells – which support immune memory and antibody response – than a shorter dosing schedule.

Current global studies into the efficacy of COVID-19 vaccines suggest that both short and long dosing schedules lead to strong real-world protection against COVID-19, emphasising the importance of having a second dose of the vaccine.

The study, named Protective Immunity from T cells to COVID-19 in Health workers (PITCH), investigated how the antibody and T cell levels change over time following either a short (three to four weeks) or long (six to 14 weeks) interval between the first and second dose of the Pfizer COVID-19 vaccine.

The research, which also involved contributions from the Universities of Liverpool, Newcastle, Sheffield, and Birmingham, examined the impacts of the Pfizer vaccine in 503 healthcare workers. 223 of these workers has previously had COVID-19. The study was funded by the Department of Health and Social Care.

Professor Susanna Dunachie, PITCH study lead from University of Oxford, said: “This work is the result of a big team effort. The study would not have been possible without collaboration between the researchers across all five universities. It has allowed us to bring clinical cohorts together and conduct one of the most in-depth analyses of the immune response to a COVID-19 vaccine yet.”

For the longer dosing interval, researchers saw antibody levels fall noticeably between the first and second dose when tested in the lab. In particular, neutralising antibody levels against the Delta variant were poorly induced after a single dose, and not maintained during the interval before the second dose. T cells were well-maintained between the first and second dose.

Antibody levels twice as high after longer dosing interval

Following two vaccine doses, neutralising antibody levels were twice as high after the longer dosing interval compared with the shorter dosing interval. Overall T cell levels were also 1.6 times lower after the long second dose, compared with the short dosing schedule. However, after the longer dosing interval, a higher proportion of T cells present were ‘helper’ T cells, which are important for long-term immune memory and help to generate antibodies to prevent infection.

The longer dosing interval resulted in higher neutralising antibody levels, after the second dose, against the Delta variant and all other Variants of Concern tested.

Differing individual responses

Researchers did note, however, that levels of antibodies and T cells varied significantly from person to person regardless of dosing schedule, which may depend on genetics, underlying health conditions, and past exposure to COVID-19 and other viruses.

The research highlights the importance of receiving two doses of the COVID-19 vaccine to maximise protection, particularly against Variants of Concern. The researchers say that a follow-up study of this cohort is needed six and 12 months after vaccination to investigate longer term immune response, as well as its potential impact on severe infection rates.

Study author Dr Lance Turtle from the University of Liverpool said: “The good news about this vaccine is that, in our laboratory-based study, everyone made very good responses, no matter what the interval between doses was. At the population level, the antibody response was a bit better in those with a longer interval between doses. These findings will help, along with other real-world data on vaccine effectiveness, to inform policy.”

Vaccines Minister Nadhim Zahawi said: “The findings from this latest PITCH study are hugely significant not just for the UK but for the world, helping us better understand the mechanics behind our immune response to COVID-19 and the importance of getting both doses of the vaccine.

“As we raced to offer a vaccine to all adults, we took the JCVI’s advice to shorten the dosing interval from 12 to eight weeks to help protect more people against the Delta variant. This latest study provides further evidence that this interval results in a strong immune response and supports our decision.

“I urge every adult to get both doses of the vaccine to protect yourself and those around you and we are looking to offer millions of the most vulnerable a booster jab from September to ensure this protection is maintained.”


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