Spike mutations in COVID-19 variants threaten vaccine efficacy

Due to mutations in the virus’ Spike protein, the antibody neutralization activity of convalescent patients with the coronavirus disease 2019 (COVID-19) seems to be attenuated against the B.1.1.7 and B.1.351 strains of SARS-CoV-2, according to a recent Singapore study.

“While governments around the world are speeding up to have COVID-19 vaccines rolled out efficiently to the majority of the population, it is of great concern that all currently approved vaccines and those still in development are based on the ancestral Spike sequence,” the researchers said.

“Our findings have shed light on the potential reduced vaccine efficacy of current COVID-19 vaccines against the emerging viral variants and highlighted the urgent need to develop new COVID-19 vaccines that are not exclusively based on the ancestral Spike sequence,” they added.

The neutralizing activity of 57 convalescent plasma samples from COVID-19 patients were tested against wildtype, B.1.1.7, and B.1.351 live virus isolates. Results revealed that samples had attenuated neutralizing efficacy against both variants relative to the virus carrying the ancestral Spike protein sequence. [NPJ Vaccines 2021;6:125]

Samples showed significant decreases in plaque reduction neutralization test (PRNT) values for the 50-, 80-, and 90-percent cutoffs. In all cases, such declines were more pronounced against the B.1.351 variant, suggesting stronger attenuation of neutralizing activity.

These findings confirmed the results of a neutralization assay against pseudoviruses containing Spike protein sequences from the wildtype, B.1.1.7, or B.1.351 strains. While most patient samples were still able to neutralize the SARS-CoV-2 at the highest concentrations, activity against both nonwildtype variants were significantly weaker.

Disease severity also appeared to be an important factor for neutralizing activity. In both the live virus and pseudovirus assays, samples taken from COVID-19 patients who had severe disease showed greater neutralizing potency against SARS-CoV-2 as compared against samples from patients with moderate or mild disease.

However, even when stratifying according to disease severity, plasma samples continued to show significantly weaker neutralizing activity against the B.1.1.7 and B.1.351 strains relative to the wildtype virus.

“The development and rapid dissemination of SARS-CoV-2 viral variants such as those originated from the United Kingdom and South Africa has generated significant concerns globally on the degree of protection afforded by humoral immune responses elicited by natural infection or vaccination,” the researchers said, adding that some studies have indeed already demonstrated significant reductions in antibody responses against these strains. [Cell 2021;doi:10.1016/j.cell.2021.03.036; Nat Med 2021;doi:10.1038/s41591-021-01294-w]

The present findings confirmed and added a Southeast Asian dimension to the growing literature on COVID-19 variants, demonstrating that the humoral immune responses elicited by initial outbreak in Singapore are weaker against emerging variants.