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In vitro study suggests COVID-19 variants might escape neutralisation by antibodies

With an increasing number of COVID-19 variants emerging, a concern is that these new variants can escape neutralisation by antibodies directed at the original strain.

The spike protein of COVID-19 binds to a cell-surface angiotensin-converting enzyme 2 receptor and this facilitates cellular entry. Given the importance for viral entry of this spike protein, many of the currently available vaccines have been developed to target the spike protein. The spike protein itself is cleaved into an S1 and S2 fragment with the former containing the N-terminal domain (NTD) and the latter the receptor-binding domain (RBD), which is the specific target for neutralising antibodies, protein-based inhibitors and serum antibodies. With currently available vaccines targeting the original spike protein on COVID-19 strains circulating in the early part of 2020, the emergence of variants such as the B.1.1.7 (UK), B.1.351 (South Africa), B.1.1.248 (Brazil) was a cause for concern, especially as these variants had substitutions in the NTD and RBD regions of the spike protein. Given the rise in variants and the possibility that available vaccines might not be effective, a team from the Department of Medicine, Washington University, US, decided to test the neutralising capacity of antibodies from different sera. The researchers obtained samples from the blood of those who had recovered from COVID-19, vaccinated with the BNT162b2 (Pfizer vaccine) and from people treated with convalescent plasma. These were then tested against a panel of authenticated COVID-19 strains with sequence variations in the spike gene including all three of the recently emerged variants.

UK variant (B.1.1.7) could be neutralised with similar antibodies levels as required for the original virus. However, with the other two variants (South Africa and Brazil) there was substantial or complete escape against antibodies from convalescent plasma and serum from individuals vaccinated with BNT162b2. Most of the reduced activity was related to a single change in the amino acid sequence of the spike protein, termed E484k which is present in both the non-UK variants but not the UK variant. Although the findings might suggest that current vaccines might not be as effective against some of the latest and emergent strains, the authors do caution that their findings are based on in vitro data and will require confirmation from in vivo studies. They suggested the need for updated antibody cocktails or adjustment to the spike sequence of vaccines to prevent loss of protection in vivo.

Chen RE et al. Resistance of SARS-CoV-2 variants to neutralisation by monoclonal and serum-derived polyclonal antibodies. Nat Med 2021