The effect of Spike mutations on SARS-CoV-2 neutralization

Antibodies produced after 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 appear, including some with large changes to the Spike protein, the target of the immune responses generated by many current COVID vaccines. Antibodies are an important part of this immune response and it is important to understand whether the antibodies generated in response to the original virus are still effective against new variants, both in terms of how wide-ranging the response is and how strong it is. 

Researchers from the UK Coronavirus Immunology Consortium and from the SAFER Consortium worked together to understand how changes to specific parts of the Spike protein of the virus would affect how well antibodies could neutralise the virus. They made small changes to the virus’ structure to produce 15 different ‘mutated’ versions of the virus. They collected antibodies from serum samples gathered from two cohorts: healthcare workers who had had mild COVID-19 symptoms, and hospitalised patients who had experienced severe COVID-19. The researchers then assessed how well these antibodies could neutralise each of the 15 ‘mutated’ viruses they had created.

The researchers found 7 changes to the Spike protein that could reduce the neutralising activity of monoclonal antibodies (many copies of one specific type of antibody), but that serum (which contains many different antibodies) neutralisation was less strongly affected. Only one of the ‘mutated’ viruses was unable to be neutralised, meaning where one specific change to the Spike protein had been made, and this was only when using one serum sample. Encouragingly, the results also suggested sizeable cross-protection against the B.1.1.7 (‘Kent’) variant, now common in the UK, was present in people who had been exposed 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 blood serum in this study 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. 

Overall, the results demonstrated that changes in the Spike protein can affect how well antibodies can neutralise SARS-CoV-2. Following the rollout of COVID-19 vaccines, and exposure through natural infection, it is possible that selective pressure could lead to further changes to the Spike protein that allow escape from neutralising antibodies. For this reason, it will be important to keep monitoring for changes to the Spike protein in new variants and assess how effectively antibodies generated to target the ‘original’ virus and vaccines are able to neutralise them.

Full details on the paper can be found on our publications page.