Scientists warn vaccine re-design is inevitable after latest findings

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SCIENTISTS have warned that the need for vaccine re-design may be inevitable after new data found a mutation that could impair neutralising antibody responses. 

The new research has found that a mutation within the virus’s spike protein receptor binding motif (RBM) frequently mutates highlighting the plasticity of the virus.

The study, was conducted by an international team of scientists including researchers at the MRC University of Glasgow Centre for Virus Research (CVR). 

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(Photo by Fusion Medical Animation on Unsplash) The new research has found that a mutation within the virus’s spike protein receptor binding motif (RBM) frequently mutates highlighting the plasticity of the virus.

The research published today in the journal Cell, shows how this change in SARS-CoV-2’s genome increases the binding affinity of the virus to the human ACE2 receptor.

The frequent occurrence of mutations within the RBM highlights the ‘plasticity’ of this part of the Spike protein, which is a major target of vaccines and therapeutic monoclonal antibodies. 

Scientists are now warning that vaccine re-design is likely and could be inevitable.

Prof Emma Thomson from the  MRC University of Glasgow Centre for Virus Research and co-author on the study comments, “The plasticity of the receptor binding motif in the spike protein of SARS-CoV-2 and the evidence that a single mutation, N439K can impair neutralising antibody responses indicates that we may need to update vaccine design in the future, particularly in the light of the emergence of new variants around the world.

“The importance of our early warning sequencing surveillance system carried out across the UK by the COG-UK consortium, is very clear.

“Understanding the impact of new variant strains that have multiple changes in the genome on vaccines is the next major challenge for the scientific community.”

The study began in June 2020, and scientists say that the relatively slow rate of evolution was giving scientists the impression that SARS-CoV-2 mutations would result in no immediate threat to vaccines or therapies. 

Senior author Prof David Robertson, MRC-University of Glasgow Centre of Virus Research, said: “The amino acid change N439K was the first RBM amino acid replacement that increased to high frequency and so can be viewed as a ‘sentinel’ mutation for SARS-CoV-2 antigenic change.

“By studying it in detail we intended to better understand the potential evolutionary trajectory of the new virus.” 

This first lineage defined by N439K was, other than a small number of cases, only observed in Scotland.

As a result of the Lockdown in the UK this lineage was driven to extinction, demonstrating that lockdowns not only decrease infection numbers but can impact on virus variation too.

At the time one other virus had been observed with the N439K mutation.

Unfortunately, these variants have now seeded the global spread of variants carrying this RBM change to more than 30 countries. 

Out of concern for the potential harm N439K variants may cause, Professor Thomson activated a clinical team to look into the clinical history of infected Scottish individuals.

Prof Emma Thomson, from the, said: “We were concerned about this mutation in 2020 because it was predicted to increase binding to the human ACE2 receptor and we were worried that it might be associated with escape from natural immunity.

“So we were initially relieved when it disappeared after the first lockdown. 

“However, it became clear the virus could mutate to avoid the immune response without losing fitness to replicate – we were able to demonstrate this in our high biocontainment laboratories through cross-competition assays at the CVR. 

To understand whether and how the N439K mutation might evade immunity, researchers at the CVR collaborated with researchers at Vir Biotechnology based in Switzerland and the USA. 

The researchers quantified the plasticity of SARS-CoV-2 RBM region and conducted detailed protein structural analysis, including solving the bound N439K-mutation-human-ACE2 structure.

Senior author Gyorgy Snell, Vir Biotechnology, said: “Looking at the how Spike’s binding interface made contact with the ACE2 receptor, it was immediately clear SARS-CoV-2 was going to accommodate further amino acid changes contributing to immune evasion and more significant changes than N439K was causing.” 

Senior author Prof David Robertson, MRC-University of Glasgow Centre of Virus Research said: The need for vaccine re-design is looking inevitable, particularly as the vaccine coverage is going to be very unevenly distributed. We urgently need a more equitable use of vaccines internationally with scale up in production and dissemination. Controlling this virus is possible but it needs a more coordinated global effort.”

The paper can be found here: https://www.cell.com/cell/fulltext/S0092-8674(21)00080-5?rss=yes