Antibodies generated following COVID-19 vaccination or infection can recognise and neutralise a range of related coronaviruses, including those found in bats, according to new research from King's College London and the Francis Crick Institute.
The findings could help guide the development of antibody treatments and vaccines designed to provide broader protection against the group of viruses known as sarbecoviruses - which include the virus responsible for the COVID-19 pandemic (SARS-CoV-2) and related viruses found in bats that could pose a future threat to humans.
Antibodies are proteins produced by the immune system in response to infection from a pathogen or a vaccine. Antibodies recognise and attach to specific targets on the surface of pathogens - some can neutralise viruses by preventing them from entering cells. If the body is exposed to the same pathogen again in the future, the body remembers to generate the antibodies needed to eliminate the infection.
However, viruses like SARS-CoV-2 evolve, producing new variants that aren't always recognised by existing antibody responses. Scientists are also monitoring related coronaviruses found in animals, particularly bats, that could potentially spread to humans. Understanding which parts of these viruses remain similar could therefore be important for developing treatments that offer broader protection against different variants and related viruses.
In the study, published in PLOS Biology, researchers examined three antibodies isolated from people who had received a COVID-19 vaccine or who had recovered from infection with SARS-CoV-2. They found that the antibodies could recognise a range of sarbecoviruses, including several viruses found in bats. They also demonstrated varying levels of neutralising activity against SARS-CoV-2 variants and other related viruses.
The work was carried out by Ayush Upadhyay, PhD student in Professor Katie Doores' group at King's and Professor Peter Cherepanov's group at the Crick.
Sarbecoviruses are a set of distinct viruses that infect mammals as varied as bats, civets and humans, among others. Despite their differences, many of them share some common vulnerabilities. Structural data from broadly neutralising antibodies could inform further iterations of vaccine design to guide immune response towards their shared Achilles heel.
Ayush Upadhyay, PhD student at King's and the Crick and lead author of the paper
To understand how the antibodies work, the team used a technique called cryo-electron microscopy, which allows scientists to examine the structure of proteins in detail. They investigated how the antibodies attach to the Spike protein found on the surface of coronaviruses, which helps the virus enter cells and is a major target for antibodies produced following infection or vaccination.
The researchers found that all three antibodies target parts of the Spike protein that have remained largely unchanged across different SARS-CoV-2 variants and related bat coronaviruses. One antibody, known as V1WT_06, was particularly effective at neutralising a broad range of viruses tested, including recent SARS-CoV-2 variants.
The researchers also investigated whether the antibodies could recognise sarbecoviruses found in bats that don't yet pose a threat to humans because they use receptors found on bat cells rather than human cells to infect cells. In the lab, they found that two of the human antibodies could recognise and neutralise two bat sarbecoviruses when they tried to infect human cells that had been modified to have bat cell receptors on their surface.
These findings suggest that immunity generated through existing COVID-19 vaccination or infection may already provide some recognition of related coronaviruses found in animals, including viruses that have not yet adapted to enter human receptors.
There is a growing concern that coronaviruses circulating in animals could potentially spread to humans. Our findings suggest that immunity generated through COVID-19 infection or vaccination may already provide some recognition of closely related bat coronaviruses, potentially making it harder for these viruses to cross over into humans.
Professor Katie Doores, Professor of Viral Immunology at King's and co-senior author of the paper
"By identifying parts of these viruses that have remained largely unchanged as they evolve, we hope to support the development of vaccines and antibody treatments that could provide broader protection against future coronaviruses," said Professor Katie Doores, Professor of Viral Immunology at King's and co-senior author of the paper.
While the findings suggest that existing immunity to SARS-CoV-2 could potentially help limit the spread of related viruses to humans, further research is needed to establish whether these antibodies could provide protection against infection.
This study was supported by funding from the UKRI Medical Research Council and the Wellcome-funded consortium Genotype-to-Phenotype Global.
