Prior SARS-CoV-2 infection primes the immune response to one dose of Pfizer/BioNTech vaccine

26th March 2021
  • People previously infected with SARS-CoV-2 show significantly higher T cell and antibody responses following a single dose of Pfizer/BioNTech vaccine compared with uninfected individuals

  • While both groups show robust immune responses after one dose, the higher response experienced by previously infected individuals likely represents a ‘boost’ to their immune defences, providing further protection against contracting COVID-19

  • Researchers from the Universities of Sheffield, Oxford, Liverpool, Newcastle, and Birmingham studied 237 healthcare workers, 113 of whom had previously been infected with COVID-19.  

  • The PITCH study, funded by the Department of Health and Social Care, supported by the UK Coronavirus Immunology Consortium, is the most in depth research in this area to date. It is published as a preprint with The Lancet.

Clinical trials report that the Pfizer/BioNTech COVID-19 vaccine is up to 95% effective against symptomatic disease after two doses.1 As well as examining effectiveness, it’s also important that we understand the underlying mechanisms of how the immune system responds to vaccination in different groups of people to allow us to optimise vaccination protocols and maximise protection against SARS-CoV-2 within our population.  This study set out to examine immune responses after one dose of the Pfizer/BioNTech vaccine in individuals with and without a previous history of SARS-CoV-2 infection.

Researchers from the Universities of Sheffield, Oxford, Liverpool, Newcastle and Birmingham studied 237 healthcare workers (median age 43, range 22-71; 78% female), 113 of whom had previously been infected with SARS-CoV-2. All participants were vaccinated with the Pfizer/BioNTech BNT162b2 mRNA vaccine. For the 124 healthcare workers who had not previously had COVID-19 (termed ‘naïve’ individuals), 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.

One dose of the Pfizer/BioNTech vaccine generated antibody and T cell responses in all but one of the 103 SARS-CoV-2 naïve participants. These responses were at a similar level or higher to those observed in individuals who had previously been infected with SARS-CoV-2 but were yet to be vaccinated. This backs up previous work showing a single dose of the Pfizer/BioNTech vaccine provides the majority of people with good protection from severe COVID-19.

After one dose of the vaccine, participants who had prior SARS-CoV-2 infection showed significantly higher antibody and T cell responses compared with SARS-CoV-2 naïve individuals, with antibody responses approximately 6.8 times higher and T cell responses approximately 5.9 times higher.  We know from the SIREN study2 that antibody responses produced following natural infection are correlated with protection against reinfection. Although more research is needed, particularly regarding the role of T cells, the immune responses observed in both study groups after one vaccine dose are compatible with the substantial protection against contracting severe COVID-19 that has been reported by the SIREN study as well as further national population-based studies from Public Health Scotland, Public Health England and Israel. The previously infected group appear to receive an extra ‘boost’ to their immune defences from vaccination, which could further decrease their risk of infection if they were to come across the virus. 

In previously infected individuals, the breadth of their T cell response expanded after vaccination to recognise more regions of the SARS-CoV-2 Spike protein. This is important as this broader response induced by vaccination could provide more robust protection against different viral variants should they be encountered.  The study also found that the high antibody responses in previously infected individuals after vaccination may also retain activity against some SARS-CoV-2 variants of concern.
In the ‘naïve’ cohort who received two vaccine doses, their T cell responses were equivalent to those observed in participants who had previously had COVID-19 after one dose. However, antibody levels were still significantly lower than those observed in participants who previously had COVID-19 after one vaccine dose. 

Overall, these findings provide an insight into the immune response generated by vaccination in both SARS-CoV-2 naïve and previously infected individuals. Following one dose of the Pfizer/BioNTech vaccine, both antibody and T cell responses are observed in the vast majority of individuals, although these were significantly higher in participants who had previously been infected with SARS-CoV-2. These findings increase our understanding of how immunity is generated by COVID vaccination and can feed into future vaccination strategies. They also provide reassurance that one dose of the Pfizer/BioNTech vaccine did elicit strong immune responses in this cohort. Further research is now needed to assess how the observed immune responses are maintained over the longer term and to increase our understanding of how they translate to real world effectiveness.


Dr Thushan de Silva, study author from the University of Sheffield, said:

“Our study is one of the largest and most comprehensive accounts of the immune response to one dose of Pfizer/BioNTech vaccine comparing previously infected and infection-naive individuals. 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.”


Professor Susanna Dunachie, PITCH study lead from the 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 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.” 


Professor Paul Moss, UK Coronavirus Immunology Consortium lead from University of Birmingham, said:

“Vaccines are a crucial part of our roadmap out of this pandemic. To maximise their impact, it’s critical that we understand the underlying biology of how they induce immunity in different groups of people.  

"When working in a pandemic, time is of the essence. This collaborative approach to science, working with multiple partners at scale, is allowing us to drive forward our knowledge at an unprecedented rate. The UK Coronavirus Immunology Consortium, working with PITCH, is a great example of how this team science approach can answer these key questions and help us hasten effective pandemic control."


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


For more information, details of the full paper are as follows: Angyal et al. 2021. T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study. Preprints with The Lancet. [DOI unconfirmed].

The full study can also be found in our publication section.


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