Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

30 April 2021

In those who have not previously been infected and have so far only received one dose of vaccine the immune response to variants of concern may be insufficient.

The findings, published today in the journal Science and led by researchers at Queen Mary University of London, Imperial College London and University College London, looked at immune responses in UK healthcare workers at Barts and Royal Free hospitals following their first dose of the Pfizer/BioNTech vaccine.

They found that people who had previously had mild or asymptomatic infection had significantly enhanced protection against the Kent and South Africa variants, after a single dose of the mRNA vaccine. In those without prior COVID-19, the immune response was less strong after a first dose, potentially leaving them at risk from variants.

‘Reassurance and a warning’

Co-lead researcher Áine McKnight, Professor of Viral Pathology at Queen Mary’s Blizard Institute, said: “Our study offers reassurance and a warning. We show that current vaccines offer some protection against variants of concern. However, people who have received only the first course of a double dose vaccine show a more muted immune response. We must ensure that the global vaccination programme is fully implemented. Current events in India make painfully clear the cost of complacency.”

Professor Rosemary Boyton, Professor of Immunology and Respiratory Medicine at Imperial College London, added: “Our findings show that people who have had their first dose of vaccine, and who have not previously been infected with SARS-CoV-2, are not fully protected against the circulating variants of concern. This study highlights the importance of getting second doses of the vaccine rolled out to protect the population.”

Insights into Kent and South Africa variants

Blood samples were analysed for the presence and levels of immunity against the original strain of SARS-CoV-2, as well as the Kent (B.1.1.7) and South Africa (B.1.351) variants of concern. Along with antibodies – the Y-shaped proteins which stick to the virus and help block or neutralize the threat – the researchers also focused on two types of white blood cell: B-cells, which ‘remember’ the virus; and T cells, which help B cell memory and recognise and destroy cells infected with coronavirus.

They found that after a first dose of vaccine, prior infection was associated with a boosted T cell, B cell and neutralizing antibody response, which could provide effective protection against SARS-CoV-2, as well as the Kent and South Africa variants.

However, in people without previous SARS-CoV-2 infection, a single vaccine dose resulted in lower levels of neutralizing antibodies against SARS-CoV-2 and the variants, potentially leaving them vulnerable to infection and highlighting the importance of the second vaccine dose.

The team looked at two variants of concern, however, they think it possible that the findings will apply to other variants in circulation, such as the Brazil (P.1) and India (B.1.617 and B.1.618) variants.

It remains unclear precisely how much protection is offered by T cells. Interestingly, the mutations in the Kent and South Africa variants here resulted in T cell immunity which could be reduced, enhanced or unchanged compared to the original strain, depending on genetic differences between people.

The importance of completing both vaccine doses

Joseph Gibbons, Research Scientist at Queen Mary’s Blizard Institute added: “This study is reassuring for those who have previously been infected. One dose of a double dose vaccine boosts their immunity, including against variants of the virus circulating in the UK. However, immunity against variants, including the ‘Kent’ variant (B.1.1.7), was much weaker in those who had only received one dose of the vaccine and had not been previously infected.”

Corinna Pade, Post-doctoral Research Scientist at Queen Mary’s Blizard Institute added: “Our study highlights that vaccines are effective. Against a backdrop of emerging variants, our findings emphasise that completing both injections of double dose vaccines is very important. It should also prompt us to monitor immune responses against variants closely in future.”

The study was carried out in collaboration with researchers at Barts Health NHS Trust, Public Health England, Royal Free Hospital NHS Trust, University College London and University of Nottingham.

The research was supported by funding from the, UKRI Medical Research Council, Rosetrees Trust and Barts Charity.

More information

• Research paper: ‘Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose’ by Reynolds, CJ. et al. is published in Science. DOI: 10.1126/science.abh1282