A longer gap between first and second doses of the Pfizer-BioNTech COVID-19 vaccine generates strong antibody and T cell immune responses, UK researchers have found. 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.
The Protective Immunity from T cells to Covid-19 in Health workers study’ (PITCH) found that 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. The studies worldwide 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.
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, said Dr Thushan de Silva, study author and Senior Clinical Lecturer in Infectious Diseases at the University of Sheffield. 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, Silva said.
The study found that overall T cell, a different type of immune cell, levels were 1.6 times lower with a long gap compared with the short dosing schedule of 3-4 weeks, but that a higher proportion were “helper” T cells with the long gap, which support long-term immune memory. The study of 503 healthcare workers published on Friday found that longer dosing intervals resulted in higher neutralising antibody levels, after the second dose, against the Delta variant and all other Variants of Concern tested.
It found that following two vaccine doses, neutralising antibody levels were twice as high after the longer dosing interval compared with the shorter dosing interval. 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.
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,” said Dr Rebecca Payne, study author from Newcastle University. However, T cell responses were consistent, indicating they may contribute to important protection against SARS-CoV-2 during this time, Payne said.
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, Payne 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, said Professor Susanna Dunachie, PITCH study lead from the University of Oxford.
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