Covid19: How Delta and Kappa variants evade immune system
A team of US scientists have explored how the mutations in Delta and Kappa variants of the Covid virus help the variants avoid recognition by antibodies. The scientists from the University of Washington School of Medicine obtained plasma samples from 37 individuals, ranging in age from 22 to 66, who had received either two doses of the Moderna or Pfizer/BioNtech or one dose of the Janssen Covid-19 vaccines.
Their data demonstrated that the Delta, Kappa, and Delta Plus variants reduced virus neutralising potency from vaccine-induced antibodies. The Delta Plus variant caused the greatest decrease. Antibodies from half of the Janssen-vaccinated individuals completely lost the ability to neutralise one or more variants in the laboratory assay.
Although the Kappa and Delta Plus variants were better able to evade vaccine-elicited antibody neutralisation, it was the Delta variant that became dominant worldwide. Vaccine developers have largely concentrated on targeting the spike glycoprotein on the surface of the Covid virus. The spike glycoprotein includes an N-terminal domain that enhances cell binding and a receptor-binding domain that engages with the ACE2 receptor on host cells.
Most antibodies against the pandemic coronavirus latch onto specific sites on these two domains. Consequently, coronavirus variants have mutated their N-terminal domain and receptor binding domain to evade these antibodies, as is the case for the delta and kappa variants, the team said.
"These are the major targets of neutralising antibodies in convalescent and vaccinated individuals, thereby raising concerns about the efficacy of available vaccines and therapeutic antibodies against these (Kappa and Delta) variants," the researchers wrote in the paper published in the journal Science.
Closely examining the structures of the main infectivity structure in the variant coronaviruses, one antibody, called S2X303, stood out because of its skill in cross-reacting with several variants, compared to all other neutralising antibodies.
By exploring how this antibody is bound to the N-terminal domain, the scientists got a clearer picture of how it attacks its target. This antibody takes an unusual angle of approach to make a unique contact footprint within the N-terminal domain.
The discovery of broadly neutralising coronavirus antibodies is also informing new Covid-19 vaccine ideas and also helping scientists to work on next-generation vaccine candidates that might be able to produce broad immunity against sarbecoviruses.
