Abstract
The successive emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has presented a major challenge in the management of the coronavirus disease (COVID-19) pandemic. There are growing concerns regarding the emerging variants escaping vaccines or therapeutic neutralizing antibodies. In this study, we conducted an epidemiological survey to identify SARS-CoV-2 variants that are sporadically proliferating in vaccine-advanced countries. Subsequently, we created HiBiT-tagged virus-like particles displaying spike proteins derived from the variants to analyze the neutralizing efficacy of the BNT162b2 mRNA vaccine and several therapeutic antibodies. We found that the Mu variant and a derivative of the Delta strain with E484K and N501Y mutations significantly evaded vaccine-elicited neutralizing antibodies. This trend was also observed in the Beta and Gamma variants, although they are currently not prevalent. Although 95.2% of the vaccinees exhibited prominent neutralizing activity against the prototype strain, only 73.8 and 78.6% of the vaccinees exhibited neutralizing activity against the Mu and the Delta derivative variants, respectively. A long-term analysis showed that 88.8% of the vaccinees initially exhibited strong neutralizing activity against the currently circulating Delta strain; the number decreased to 31.6% for the individuals at 6 months after vaccination. Notably, these variants were shown to be resistant to several therapeutic antibodies. Our findings demonstrate the differential neutralization efficacy of the COVID-19 vaccine and monoclonal antibodies against circulating variants, suggesting the need for pandemic alerts and booster vaccinations against the currently prevalent variants.
Highlights
The rapid and nearly unrestricted global spread of coronavirus disease (COVID-19) has resulted in the evolution of various mutants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)
We recently developed a rapid neutralizing test, hiVNT, which enables the detection of SARS-CoV-2 neutralizing antibodies in sera within 3 h [11, 12]
Based on the number of cases, the momentum, and immune escaping codons or mutations [17–20], we evaluated the number of immune-escape variants and the momentum to identify the best candidates for neutralization tests (Figure 1A)
Summary
The rapid and nearly unrestricted global spread of coronavirus disease (COVID-19) has resulted in the evolution of various mutants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). With vaccines being the principal effective modality to curtail the pandemic, it is crucial to use them effectively and prepare for a rise in the number of immune-escape mutants that can evolve. Immune-Escape Variants of SARS-CoV-2 due to the selection pressure exerted. Based on their clinical and epidemiological significance, the World Health Organization (WHO) has identified variants of concern (Alpha, Beta, Gamma, and Delta), variants of interest (Lambda and Mu), and variants under monitoring [1]. The Delta strain is the principal mutant responsible for the majority of the infections currently, variants with a few more amino acid substitutions in the Delta spike are emerging. Previous studies have shown that mRNA vaccines such as BNT162b2 and mRNA-1273 confer robust protection against SARS-CoV-2 [2]. There has been no temporal and comprehensive study of neutralizing activities against the increasing number of delta derivatives
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