April 12-18 2021
The South African variant is more resistant to vaccines
Development of current vaccines against COVID-19 has required a huge amount of investment. There are now four available in Europe: Pfizer-BioNTech, Moderna, Oxford-AstraZeneca and Janssen. All are designed to prompt antibody and lymphocyte T responses against the surface spike (S) protein that was present in the original Wuhan strain of the virus. In recent months, however, new variants have emerged, notably the UK, South African and Brazilian variants, which contain respectively 9, 10 and 12 mutations in the S protein. One region of the S protein requires particular attention: this is the RBD domain, which is in contact with the ACE2 cellular receptor that enables entry of the viral particle into the cell.
The Brazilian and South African variants share 3 mutation sites in this domain: K417N (South African) or T (Brazilian), E484K and N501Y. The UK variant has just one mutation, N501Y. The RBD region is the main target of neutralizing antibodies. Mutations in this domain may, therefore, lead to antibody evasion. Researchers at the University of Oxford have analysed neutralization of the Brazilian variant by antibodies directed against the original Wuhan strain. It was shown that it is less resistant to vaccination than the South African variant.
The researchers began by measuring the effectiveness of interaction between the RBD domain and the ACE2 receptor in the UK variant (N501Y) and the South African and Brazilian variants (K417N or T, E484K and N501Y) by comparing them to the original strain. An improved affinity for the cellular receptor can lead to the virus being more transmissible, and may therefore enable these variants to become dominant. They observed that interaction was 7 times higher in the UK variant and 19 times higher in the South African and Brazilian variants.
The researchers then tested the effectiveness of interaction and the neutralization potential of 20 monoclonal antibodies that block the interaction between the RBD domain and the ACE2 receptor. Only one antibody (mAb 222) was effective against the 3 variants, while 19 others proved to be less effective, especially against the South African and Brazilian variants. They repeated the tests with therapeutic antibodies developed against SARS-CoV-2. Overall, neutralization by these antibodies was reduced in the case of the UK variant, and virtually zero against the South African and Brazilian variants.
The researchers also tested neutralization using the plasma, containing antibodies, of patients who had been infected by the original strain. It seems that the Brazilian variant is 3 times less effectively neutralized in comparison to the original strain of the virus.
Finally, they tested neutralization using the serum of patients immunised with the Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Neutralization of the Brazilian variant, like the UK variant, seems to be between 2,6 and 2,9 times less effective (with the Pfizer-BioNTech for Oxford-AstraZeneca vaccines) in comparison to the original strain. And neutralization against the South African variant is even more reduced (between 7,6 and 9 times less effective).
In conclusion, the Brazilian variant seems to evade a large number of neutralizing monoclonal antibodies, but it is less resistant than the South African variant to antibodies originating from vaccination. The recent emergence of other SARS-CoV-2 variants would seem to necessitate the development of new vaccines.