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expert reaction to two preprints looking at a single dose of mRNA vaccines in those who have previously been infected with SARS-CoV-2

Two preprints, unpublished non-peer reviewed studies, look at giving a single dose of COVID-19 mRNA vaccine to those who have previously been infected with SARS-CoV-2.


Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“These two papers describe exactly what the science would predict. 

“Prime-boost vaccines work by mimicking natural immunity. The first time we encounter a new pathogen (disease-causing organism) it can take time for the immune system to generate antibodies and other aspects of the immune system that will recognise the pathogen and destroy or neutralise it, and to create memory cells that will recognise it if it is encountered again.

“And, if it is encountered again, the immune system is “primed”. B cells are ready, very rapidly, to produce large quantities of antibody; killer cells are ready to destroy it… And, in the encounter, the readiness is boosted, enhancing both the quality and the duration of immunity to the pathogen.

“This is the “prime-boost” approach taken with the vaccination.

“Some natural infections will stimulate the immune system more effectively than vaccines do – certainly, they will contain a wider range of antigens than many vaccines, which might help with cross-protection against closely related pathogens. But many vaccines, perhaps counterintuitive, work more effectively than natural infection, particularly when they are conjugated with more stimulating antigens (as with eg Hib, meningococcal, and some pneumococcal vaccines), or “adjuvanted” with other molecules that enhance the immune effect of the vaccine. 

“It is no surprise at all that a first dose of vaccine, when given to people whose immune system is already primed by natural infection, will have a booster effect very similar to the effect when given as a second, “booster” dose. 

“The reason why it was, in some cases, even more effective could be because the initial priming effect of the natural infection was more effective than the priming effect of a vaccine per se; but it could also be due to, for example, the timing. We know that booster doses increase in efficacy as the prime-boost interval increases. (There’s good reason to expect that the 12-week prime-boost interval recommended in the UK will lead to stronger, longer lasting immunity than the shorter doses recommended by the manufacturers.) And heterologous boosting, using a different product, may be more effective than a repeat dose of the same vaccine – similar effects may be arising when the priming is provided by natural infection.

“We sometimes talk about “natural boosting” from exposure to disease; but here we are considering natural priming.

“Given the observed efficacy of natural disease in priming the immune system, and thus of the first dose of vaccine following natural infection, the authors suggestion that – at least until vaccine supplies are far more abundant – it would be entirely rational to focus second, booster doses of vaccine on people who have not had natural priming, sparing badly-needed doses for boosting the immunity of people who have do not benefit from this natural priming effect.”


Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“The data presented in these two papers are not surprising but are very reassuring. Both papers show that a previous infection with SARS-CoV-2/COVID-19 primes the immune system to make a very robust response to a single dose of COVID-19 vaccine. 14 days after a single dose of vaccine, people who had a PCR-confirmed prior COVID-19 infection, or who had pre-existing anti-COVID-19 antibodies consistent with having had a prior infection, had antibody concentrations that were as high as (or up to 10 times higher) than the levels seen in uninfected people who had received two doses of the vaccine (Krammer et al) and 10 times higher than people who had been hospitalised with severe COVID-19 (Saadat et al). These data indicate that the vaccines are very effectively boosting the immunity induced by infection.

“The authors of both papers suggest that people who have had a PCR-confirmed COVID-19 infection may only require one dose of the vaccine. Certainly, this would appear to provide them with protection that is at least as good as two doses of vaccine. However, incorporating this into a mass vaccination programme may be logistically complex and it may be safer, overall, to  ensure that everyone gets two doses.

“The paper by Krammer et al also showed that people who had been infected prior to vaccination were more likely to experience ‘flu-like symptoms (fatigue, chills, headache) in the days after their vaccination suggesting that their cellular immune system was also being restimulated.  This is good to know and will allow health care workers to warn people that they are more likely to feel a little off colour for a day two after their vaccination if they have previously been infected and to reassure them that this is nothing to be concerned about.”


Prof Lawrence Young, Virologist and Professor of Molecular Oncology, University of Warwick, said:

“Is one vaccine jab enough in individuals previously infected with SARS-CoV-2? This preprint shows that the antibody response to the virus after the first dose of a mRNA vaccine in individuals with pre-existing immunity due to a previous infection is equal or greater than that induced by two doses of the vaccine in uninfected individuals. It also shows that side effects are significantly higher in response to vaccination if you have had a previous infection. The antibody levels in previous infected individuals were rapidly elevated in response to a single vaccination reaching 10-20 times those observed in those who were vaccinated without evidence of previous infection. Vaccine recipients with pre-existing immunity experienced systemic side effects with a significantly higher frequency than antibody naïve vaccines (e.g., fatigue, headache, chills, fever, muscle or join pains). This suggests that the first vaccine dose is serving as a boost in naturally infected individuals giving levels of protective immunity equivalent to that achieved with two vaccine doses in individuals who haven’t been previously infected. This means that we should be doing further studies which look at giving previously infected individuals one dose of an mRNA vaccine. If future work can confirm this high level of immunity post a single mRNA vaccine in this group of individuals, this could become a viable option when there are concerns around vaccine supply.”



Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2

Saman Saadat, Zahra Rikhtegaran-Tehrani, James Logue, Michelle Newman, Matthew B Frieman, Anthony D. Harris and Mohammad M. Sajadi

medRxiv. posted 1 February 2021, 10.1101/2021.01.30.21250843


Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine

Florian Krammer, Komal Srivastava, PARIS team and Viviana Simon

medRxiv. posted 1 February 2021, 10.1101/2021.01.29.21250653



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Eleanor Riley: “No Conflicts of Interest to declare.”

None others received.

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