A team of scientists from Japan has recently investigated the neutralizing potency of convalescent sera against currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations. The study’s findings reveal that the variants containing Y543F or N501Y spike mutations are capable of evading neutralization by SARS-CoV-2-induced antibodies. However, no such immune evading potency has been observed for the variants with only the E484K spike mutation.
The study was conducted on 41 SARS-CoV-2-positive patients. Using ELISA, the plasma samples collected from the participants were analyzed for IgG-specific antibodies against original RBD and RBD variants containing Y453F, N501Y, or E484K mutation. The structural analysis results revealed that the original three-dimensional structure of spike protein is not altered by the Y453F, N501Y, and E484K RBD mutations. Moreover, compared to the original RBD, only a slight increase in affinity of the E484K RBD was observed for the human angiotensin-converting enzyme 2 (ACE2) receptor.
Regarding antibody binding, three out of six tested antibodies showed a relatively weaker affinity for the E484K RBD compared to that for the original RBD. In contrast, one antibody showed a stronger binding affinity for the mutant RBD compared to the original RBD. Regarding the Regeneron Pharmaceuticals-developed antibody cocktail therapy, REGN-COV2, which contains two neutralizing antibodies, Casirivimab and Imdevimab, a weaker affinity was observed for E484K RBD compared to that for the original RBD. In 29 out of 41 COVID-19 positive patients, serum IgG-specific antibodies showed strong neutralizing affinity toward original RBD. Similarly, strong and moderate levels of neutralizing affinities for E484K RBD were observed in 16 and 10 COVID-19 patients, respectively.
Regarding RBD Y453F mutant, serum IgG-specific antibodies with strong and moderate neutralizing affinities were detected in 1 and 6 COVID-19 patients, respectively. Similarly, a moderate neutralizing affinity of serum IgGs toward the RBD N501Y mutant was observed in 8 out of 41 patients. Taken together, these observations indicate that Y453F and N501Y mutations in the spike RBD have a higher impact than the E484K RBD mutation in reducing the neutralizing potency of IgG-specific antibodies developed in response to natural SARS-CoV-2 infection.
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