Antibodies generated following infection with the original SARS-CoV-2 virus circulating in spring 2020 are likely still able to effectively neutralise the Kent (B.1.1.7) variant, a new study by UK-CIC researchers has shown. However, protection against this variant is not as ‘robust’ as to the original. This study is published in the journal Cell Reports.
Variants of the SARS-CoV-2 virus continue to emerge, including some with significant changes to the Spike protein, the target of immune responses generated by many current COVID vaccines. Antibodies are a core component of this immune response and it is important to assess whether those generated in response to the original virus are still effective, both in terms of breadth of response and potency, against new variants.
Researchers from the UK Coronavirus Immunology Consortium and from the SAFER Consortium worked together to understand how changes to specific amino acids in the Spike protein of the virus would affect the neutralising activity of antibodies. They made small changes to amino acids in the virus’ structure to produce 15 types of ‘mutated’ virus. They then tested the neutralising activity of antibodies in serum samples from two cohorts: healthcare workers who had had mild COVID-19 symptoms, and hospitalised patients who had experienced severe COVID-19.
The researchers found 7 changes to the Spike protein that could reduce the neutralising activity of monoclonal antibodies, but that serum neutralisation was less strongly affected. There was only one engineered change identified that completely abolished neutralising activity and this was only in one serum sample. Encouragingly, the results also suggested substantial cross-protection against the B.1.1.7 (‘Kent’) variant, now common in the UK, was present in those with exposure to the original SARS-CoV-2 virus. However, changes to regions of the Spike protein did mean this protection was not as robust.
The researchers say that antibody responses were likely more effective in sera because there are a wide range of antibodies present that bind to many different sites of the Spike protein. In comparison, monoclonal antibodies are specific to one region, so a change to that region would have a much larger effect on their ability to neutralise the virus. This means that, in a real-world immune response, a change in one region would not stop all types of antibodies present from being able to neutralise the virus.
The results demonstrated that changes in the Spike protein can affect the ability of antibodies to neutralise SARS-CoV-2. Following vaccine rollout, and exposure through natural infection, it is possible that selective pressure could cause further changes to the Spike protein that allow escape from neutralising antibodies. It is therefore important to continue to monitor the changes to the Spike protein in new variants and assess how effectively antibodies from exposure to the ‘original’ virus and vaccines are able to neutralise them.
This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC), funded by UK Research and Innovation and NIHR. Our grateful thanks go to all the patients who volunteered to take part in this study.
For more information, details of the full paper are as follows: Rees-Spear et al. 2021. The effect of spike mutations on SARS-CoV-2 neutralization. Cell Reports.