A new study led by the Universities of Sheffield and Oxford with support from the UK Coronavirus Immunology Consortium (UK-CIC) has found that 99% of people generate a robust immune response against COVID-19 after just one dose of the Pfizer vaccine.
The Protective Immunity from T cells to Covid-19 in Health workers study (PITCH) examined how the immune system responds to COVID-19 after one dose of the Pfizer vaccine among people who have been infected by COVID-19 before and those who have not.
It suggests one dose of the vaccine protects against severe disease, supporting the decision to delay the second dose and provide protection to as many higher-risk groups as possible by providing more first doses. The study showed after two doses levels of protection were even stronger, underlining the importance of people coming forward for their second dose.
Between 9 December 2020 and 9 February 2021, researchers from the Universities of Sheffield, Oxford, Liverpool, Newcastle and Birmingham analysed blood samples from 237 healthcare workers to understand their T cell and antibody responses following vaccination from the Pfizer vaccine.
The study, which in Sheffield was supported by Sheffield Teaching Hospitals NHS Foundation Trust, also sheds light on the impact of previous infection from COVID-19 on people’s immune response to vaccination. It found that people who had previously been infected with COVID-19 showed higher T cell and antibody responses after one dose of the Pfizer vaccine compared with people who had never had COVID-19 before and had one dose of the vaccine.
The researchers discovered that among people who had had CCOVID-19 in the past, the T cell response expanded after vaccination to recognise more regions of the COVID-19 spike protein – which attacks the immune system and causes severe disease. This means, even in those already infected, vaccination from the Pfizer jab provides better protection and an enhanced immune response to COVID-19 than the immune response from natural infection, further supporting the need for a vaccination programme.
It is not yet known how long T cell and antibody response lasts following infection. The first dose of both the Pfizer and AstraZeneca vaccine offer good levels of protection, but to get maximum protection it is vital everyone gets a second dose when invited as two doses of the vaccine will provide longer-lasting protection from the virus.
Lead academic of the study, Dr Thushan de Silva, senior clinical lecturer in infectious diseases at the University of Sheffield and honorary consultant physician in infectious diseases at Sheffield Teaching Hospitals Foundation Trust, said: “Our results demonstrate that T cell and antibody responses induced by natural infection are boosted significantly by a single dose of vaccine. While the response to a single dose was lower in infection-naïve individuals, it was still equivalent or better than the immunity in previously infected individuals before it is boosted by vaccination.”
PITCH lead, Professor Susanna Dunachie, NIHR global research professor at the Nuffield department of medicine, University of Oxford, said: “Our study highlights the importance of studying both aspects of immune protection when trying to understand the underlying mechanisms of the immune response to COVID-19 vaccination.
“Interestingly, we also found that vaccination improves the breadth of T cell responses generated in previously infected individuals. In immunology, this is a good thing as it means that you are more likely to maintain protection against new mutations of the virus, and further work will assess how long these vaccine responses last. It’s still important that everyone follows National Health Service (NHS) guidelines to get two doses of the vaccine, even if you think you may have previously had COVID-19.
“The PITCH Study has been a great opportunity to work collaboratively across five university hospitals and with Public Health England to look at T cell responses to SARS-CoV-2 at greater scale and depth than a single research centre can. By building on the national SIREN Study and putting our heads together, we are contributing towards illuminating the role of T cells in protection against COVID-19 from vaccines and previous infection.”
Professor Paul Klenerman, PITCH study lead from the University of Oxford, said: “T cells are an important component of immunity to viruses – but typically much harder to measure than antibodies. To set this up at scale across the UK in the midst of a pandemic was a big challenge but the very clear data found by PITCH show just how informative this approach can be.”
UK Health and Social Care Secretary Matt Hancock, said: “The PITCH study presents further proof that vaccines provide excellent protection against the virus. Thanks to the incredible efforts of our vaccination programme, over half of all adults in the UK have had the jab, and we remain on track to offer all adults a vaccine by the end of July.
“The vaccine has already saved thousands of lives in the UK. A second vaccine jab is crucial for longer-term protection, regardless of whether you have previously had Covid-19 or not, and I urge everyone to make sure they attend their second appointment – to keep themselves and those around them safe.”
Health Minister Lord Bethell, said: “These findings from the PITCH study are crucial to increasing our understanding of the immune response to Covid-19 and how the Pfizer vaccine is working to protect people across the UK already. “I urge everyone to come forward to be vaccinated when invited and to take up both doses of the vaccine as both are vital to ensuring long term protection from COVID-19.”
Among individuals who had not had COVID-19 in the past and had received two doses of the Pfizer vaccine, T cell response was as strong as people who had had previous COVID-19 infection and one vaccine dose; after one dose of the Pfizer vaccine, individuals who had previous COVID-19 infection showed higher antibody and T cell responses compared with people who had not been infected before. Antibody responses were 6.8 times higher and T cell responses 5.9 times higher; among individuals who had not had COVID-19 in the past and had received one dose of the Pfizer vaccine, antibody and T cell responses were at a similar or higher level compared to those who had previously been infected but not been vaccinated; and there was no link between age and levels of T cell/antibody response.
An effective vaccine is one that saves lives and reduces hospitalisations. Both the Pfizer and Oxford-AstraZeneca vaccines have been shown to be highly effective in reducing COVID-19 infections among older people aged 70 years, according to previously published research carried out by Public Health England. In the over 80s, data suggest that a single dose of either vaccine is more than 80 per cent effective at preventing hospitalisation, around three to four weeks after the jab.
Further research will continue to deepen our understanding of the immune responses over the longer term and what it means for protection against COVID-19 in the real world.
Even after vaccination everyone must continue to follow the rules – remembering hands, face, space – as it may still be possible to pass the virus on to others after having the jab.
This study formed part of the PITCH Study (Protective Immunity from T-cells in Healthcare workers), which was funded by the UK’s department of health and social care. A contribution was also made from the UK Coronavirus Immunology Consortium (funded by UK Research and Innovation and the National Institute for Health Research).
Of the 237 healthcare workers, 113 had previously been infected with COVID-19 compared to 124 healthcare workers who had not. For those who had not previously had COVID-19, 103 were given one dose of the vaccine and 21 were given two doses, with a gap of 23 days between doses.
The researchers took blood samples from participants prior to and 28 days after vaccination to measure various aspects of the immune response, including antibodies and T cells. A range of analyses were used to examine aspects of the T cell response including the magnitude of response and the response to different proteins from SARS-CoV-2.
Carrying out these T cell analyses is much more complex than antibody studies and difficult to undertake at scale – but this study is the largest and most in depth in the world to date in this field.
Do antibody positive healthcare workers have lower SARS-CoV-2 infection rates than antibody negative healthcare workers? Large multi-centre prospective cohort study (the SIREN study), England: June to November 2020
V Hall, S Foulkes, A Charlett, A Atti, EJM Monk, R Simmons, E Wellington, MJ Cole, A Saei, B Oguti, K Munro, S Wallace, PD Kirwan, M Shrotri, A Vusirikala, S Rokadiya, M Kall, M Zambon, M Ramsay, T Brooks, SIREN Study Group, CS Brown, MA Chand, S Hopkins
Published in medRxiv
There is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection.
A large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis.
Between 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days.
A prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included.
Department of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.
Competing Interest Statement
The authors have declared no competing interest.