Greater cross-neutralization against UK SARS-CoV-2 variant in vaccinated individuals with prior infection

A team of researchers in Spain has observed that, of those who have been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), higher titers of neutralizing antibodies for the B.1.1.7 variant (originating in the UK) were present in those who had previously been infected with the virus.

While it remains unknown how long vaccine-induced immunity lasts, these findings support the notion that a delay in vaccinating those with antibodies from prior (or natural) infection could expediently boost coverage of population immunity.

The study authors write:

Our data suggest that previous infection contributes to a better neutralization of B.1.1.7 variant in vaccinees, being the uninfected vaccinees the individuals showing a more evident, although small in magnitude, loss of neutralization."

The study "Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals" is available as a preprint on the bioRxiv* server, while the article undergoes peer review.

Features of the B.1.1.7 variant

The B.1.1.7 variant was first detected in England last October (2020) and has since become the UK's dominant strain. Current research shows the variant has several genetic mutations compared to previous strains.

The N501Y mutation on the receptor-binding domain (RBD) of the virus's spike protein – the means by which it infiltrates host cells – likely contributes to the variant's increased transmissibility. The P681H mutation is potentially involved in viral infection.

The bright side is that these genetic mutations do not appear to translate to more severe disease. Additionally, there is some evidence of neutralizing antibodies being effective against the B.1.1.7 variant.

With this in mind, the study investigated which method — natural infection from previous coronavirus strains or vaccination — creates the greatest amount of neutralizing antibodies.

Study methods

The researchers created pseudoviruses with preexisting SARS-CoV-2 strains that have caused outbreaks. This included the coronavirus variant that initially appeared in Wuhan, China, in December 2019. Others had the D614G strain that caused the pandemic outbreak in Europe and the recent B.1.1.7 variant in the UK.

The researchers collected plasma samples from 32 individuals 48 or 196 days after SARS-CoV-2 infection (in March 2020) to evaluate the amount of neutralizing antibodies available.

The researchers also collected plasma samples from 16 individuals 44 days after they first showed symptoms of COVID-19, and about 5 of which had been infected with the B.1.1.7 SARS-CoV-2 variant.

The last group involved 32 individuals who were either previously infected or never infected and who had received both doses of the Pfizer-BioNTech vaccine. Plasma samples were taken 2 weeks after the second dose. A total of 98 plasma samples were tested against the three coronavirus pseudoviruses.


Vaccinated individuals had more ability to neutralize the preexisting European strain, D614G.

People who received neutralizing antibodies from prior infection also showed greater potency in neutralizing the D614G mutant.

The researchers decided to further evaluate the immune response differences by analyzing infected and vaccinated subgroups.

They found people with prior infection from the first wave in Spain were 60% more likely to have had the D614 strain. Meanwhile, people previously exposed to SARS-CoV-2 during the second wave were most exposed to G614-containing 20E(EU1) lineage.

People infected during the first wave showed no difference in neutralizing activity when confronted with the B.1.1.7 variant.

A direct comparison of these median fold-changes showed statistically significant difference between groups indicating that time from infection modulates changes in cross-neutralization activity. This observation supports the positive evolution overtime of neutralizing responses in infected individuals suggested by different authors," wrote the researchers.

People exposed to SARS-CoV-2 during the second wave also showed no difference in neutralizing titers between the three viruses.

Greater neutralizing ability in natural coronavirus infection rather than vaccinated

When previously exposed individuals were compared to vaccinated individuals, the researchers found that both groups showed a decreased immune response when confronted with the B.1.1.7 variant.

People with prior infection also showed more antibodies against the B.1.1.7 variant compared to vaccine-induced antibodies.

Study limitations

Given the first wave occurred in March 2020 and the second wave around August 2020, further studies that narrow the timeline and reduces variability will be needed to confirm results.

While antibodies were still present 6 months after the first wave, the researchers note that data is currently limited on how sustainable vaccine-induced immunity — including quality of antibodies or durability — will last.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Jocelyn Solis-Moreira

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.


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