Longer interval between Pfizer vaccine doses boosts immunity

One of the world’s most in-depth studies into COVID-19 immune response to vaccines shows both short and long dosing schedules of the Pfizer COVID-19 vaccine generate strong antibody and T cell immune responses.

The new preprint study involving University of Liverpool researchers found that after two doses, the longer dosing interval led to higher antibody levels and a higher proportion of ‘helper’ T cells, which support immune memory and antibody response.

Importantly, worldwide studies are showing that both the 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 Protective Immunity from T cells to COVID-19 in Health workers (PITCH) study examined how antibody and T cell levels change over time following either a ‘short’ (3–4 weeks, average of 24 days) or ‘long’ (6–14 weeks, average of 70 days) interval between the first and second dose of the Pfizer COVID-19 vaccine. Of the 503 healthcare workers recruited to the study, 223 (44%) had previously had COVID-19.

Key findings:

• For the longer dosing interval, antibody levels fell 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.
• Following two vaccine doses, neutralising antibody levels were twice as high after the longer dosing interval compared with the shorter dosing interval.
• After two doses, overall T cell levels were 1.6 times lower after the long 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 helping 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.

Regardless of the dosing schedule, the study found levels of antibodies and T cells varied significantly from person to person, which may depend on genetics, underlying health conditions, and past exposure to COVID-19 and other viruses.

This underlies the importance of everyone getting two doses of the COVID-19 vaccine to maximise their own protection, particularly against Variants of Concern. Follow up of this cohort 6 and 12 months after vaccination is needed to investigate longer term immune response, as well as whether it translates to lower or less 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.”

The study was funded by the Department of Health and Social Care and led by the University of Oxford in collaboration with the Universities of Liverpool, Newcastle, Sheffield and Birmingham, with support from the UK Coronavirus Immunology Consortium.

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.”

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 8 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 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.”

Real world data from Public Health England demonstrates the Pfizer COVID-19 vaccine is effective at reducing levels of serious disease, hospitalisation and death, even after one dose. Understanding the underlying immune response generated by different dosing schedules will help maximise future protection, tackle new Variants of Concern and prevent reinfections.

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