23 July 2021

Longer interval between the first and second Pfizer vaccine boosts antibody levels and ‘helper’ T cells

A new study published today (23 July 2021) shows both short and long dosing schedules of the Pfizer Covid-19 vaccine generate strong antibody and T cell immune responses.

Person receiving vaccine
  • One of the world’s most in-depth studies into Covid-19 immune response to vaccines shows both a short 3-week dosing interval and long 10-week dosing interval of the Pfizer vaccine generated strong antibody and T cell immune responses
  • Findings from DHSC-funded PITCH study demonstrate 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 respons
  • Results reflect how the immune response generated by the Pfizer vaccine provides real-world protection against Covid-19

A new study, which published today as a pre-print on ‘Cell Press Sneak Peak, by the Universities of Sheffield, Oxford, Liverpool, Newcastle, and Birmingham, with support from the UK Coronavirus Immunology Consortium, shows both short and long dosing schedules of the Pfizer Covid-19 vaccine generate strong antibody and T cell immune responses.

It is one of the most comprehensive studies into the immune response generated by the Pfizer Covid-19 vaccine to date, and has 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. This is 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) was supported by Sheffield Teaching Hospitals NHS Foundation Trust, and examined how antibody and T cell levels change over time following either a ‘short’ (three - four weeks, average of 24 days) or ‘long’ (six - 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 per cent) 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 six 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.

Dr Thushan de Silva, study author, Senior Clinical Lecturer in Infectious Diseases at the University of Sheffield’s Department of Infection, Immunity and Cardiovascular Disease, and Honorary Consultant Physician in Infectious Diseases at Sheffield Teaching Hospitals NHS Foundation Trust, said: “Our study shows the value of studying both antibody and T cell responses following SARS-CoV-2 vaccine, particularly to understand the multiple mechanisms of protection there may be against new Variants of Concern.

“The longer dosing interval that the UK has adopted appears to result in higher antibody levels after the second dose when compared to the shorter interval. However, there is a significant drop in antibody levels during this extended interval, while T cell responses are maintained. What is very clear is that two doses are required to maximise protection, particularly against the Delta variant. We will continue a follow up of our cohorts to assess the durability of vaccine responses and contribute to discussions around the need for booster doses.

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.

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: “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.”

Our grateful thanks go to all the healthcare workers who volunteered to take part in this study.


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