The scientists produced 18 types of pseudo-virus, consisting of different combinations of the 8 mutations found in the spike protein of the South-African variant, compared to the basal variant (which carries only the D614G mutation).
The researchers first of all tested the capacity of these different mutant viruses to infect cells. No significant difference was observed in the infectivity of these different mutations as compared to the basal strain. They then checked the sensitivity of these variants to monoclonal neutralizing antibodies. The majority of the monoclonal antibodies had weaker neutralization activity with the mutant viruses as compared to the basal viral strain. The researchers observed that the number of mutations in the RBD (the domain that interacts with the ACE2 cellular receptor to enable the entry of the viral particle into the cell) correlates to the aptitude of the virus to escape antibody actions. E484K and N501Y were shown to be the principal mutations responsible for this weakening of neutralization effectiveness. Position 484 corresponds to an important epitope (a region targeted by antibodies) and has been the subject of numerous mutations already described (E484A, E484G, E448D and E484K). However, the K417N mutation may cause greater sensitivity to neutralization: it could enhance the stability of an “open” conformation of the S protein, making this region more accessible to antibodies.
The results of this study show a reduction in neutralization of the South African variant by antibodies. This may be a worrying factor in relation to the effectiveness of vaccines developed against the basal strain of SARS-CoV-2. However, this study is based only on pseudotype viruses that are used as a study model and may not reflect the behaviour of a complete replicating virus.