A new study carried out in collaboration with the University of Birmingham shows both short and long dosing schedules of the Pfizer COVID-19 vaccine generate strong antibody and T cell immune responses.

The study, led by the University of Oxford, in collaboration with the Universities of Birmingham, Newcastle, Liverpool, Sheffield, and supported by the UK Coronavirus Immunology Consortium, is one of the most comprehensive studies into the immune response generated by the Pfizer COVID-19 vaccine to date.

It found T cell levels are well-maintained and antibody levels are higher following a longer interval between the first and second dose of the Pfizer COVID-19 vaccine, despite a significant drop in antibody levels between doses. 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 study (PITCH) 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.

The study results are being published as a pre-print on ‘Cell Press Sneak Peak’ and have therefore not yet been peer reviewed.

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.”

Professor Paul Moss, Principal Investigator of the UK Coronavirus Immunology Consortium and Professor of Haematology at the University of Birmingham, said: “This is an important study that reveals how changing the interval between doses of the COVID-19 vaccine has a significant effect on the immune response generated. It also demonstrates the benefit of a team science approach that brings researchers together to understand key questions on the immunology of COVID-19. The UK Coronavirus Immunology Consortium has been incredibly successful in fostering new partnerships like this.”

Alex Richter, Professor in Clinical Immunology at the University of Birmingham, said: “Real world data demonstrates the Pfizer COVID-19 vaccine is effective at reducing levels of serious disease, hospitalisation and death. There is benefit after one dose but two doses provides a much more robust response. Understanding the underlying immune response generated by different dosing schedules will help maximise future protection, tackle new Variants of Concern and prevent reinfections.”

Dr Rebecca Payne, study author from Newcastle University, said: “Our study is one of the most comprehensive assessments of the immune response to SARS-CoV-2 following two doses of the Pfizer vaccine. We found an interesting pattern in the levels of immune cells present. Our study provides reassuring evidence that both dosing schedules generate robust immune responses against SARS-CoV-2 after two doses. For the longer schedule, the antibody levels dropped off between first and second dose, which included the loss of any neutralising effect against the Delta variant. However, T cell responses were consistent, indicating they may contribute to important protection against SARS-CoV-2 during this time. After the second dose on the longer dosing schedule, antibody levels surpassed those seen at the same time point after a shorter dosing interval. Although T cell levels were comparatively lower, the profile of T cells present suggested more support of immune memory and antibody generation. We now need to carry out more follow up studies to understand the full clinical significance of our findings.”

Professor Susanna Dunachie, PITCH study lead from University of Oxford, said: “We know that the Pfizer COVID-19 vaccine is very effective at preventing serious disease, even after one dose, but we don’t yet understand what the exact immune response is that underlies this effect. Our study aimed to shine a light on the different type of immune cells involved to help us better understand the potential mechanisms of protection, particularly against new Variants of Concern. It is clear from our findings that to maximise your individual protection, it is very important to get two doses of the COVID vaccine when offered.

“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.”