March 03, 2021
Researchers have recently published findings that show the deletion of the spike protein of SARS-Cov-2 in the N-terminal domain (NTD). The NTD deletion prevents neutralization of the coronavirus by antibodies, and this might contribute to new variants.
Scientists expected SARS-CoV-2 to evolve slowly since its appearance, but the virus copies its large RNA genome with a polymerase that also corrects errors, thus reducing mutations.
This genomic steadiness was believed to be good news for the design of vaccines, but as variants such as B.1.1.7, B.1.351 started to appear, it was clear that SARS-CoV-2 is mutable and could fight neutralizing antibodies. Scientists discovered that SARS-CoV-2 tends to delete portions of RNA that encode the NTD of the spike, a mutation that its proofreader cannot discover. These findings might shed light on how new forms of SARS-CoV-2 occur and avoid detection of antibodies by the host immune system.
Scientists then checked whether six of these deletions would be able to disrupt the binding of antibodies. The ability of an antibody previously isolated from a convalescent patient to neutralize the virus was eliminated by three of those deletions and one deletion combination in the NTD. This particular antibody lost its potency, but both variants were neutralized by the convalescent serum, which contained a full range of antibodies.
Variants and vaccine efficacy of NTD deletion
According to a COVID-19 vaccine candidate tracker released by the World Health Organization on 12 February 2021, 11 vaccines initiating immunity to only the receptor-binding domain (RBD) of the spike, which must attach to the ACE2 receptor to enter the host cells, are at different levels of clinical trials.
Only time will tell the best strategy for vaccine development - the use of RBD-directed antibodies or the inclusion of NTD-directed antibodies as well.
References:
K.R. McCarthy et al., “Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape,” Science, doi:10.1126/science.abf6950, 2021.
https://www.the-scientist.com/news-opinion/sars-cov-2-with-genomic-deletions-escapes-an-antibody-68453
Luciana Aparecida Campos Baltatu, Ph.D.
College of Health Sciences
Abu Dhabi University
