SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity
SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity
Abstract The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. The spike proteins of B.1.617.1, B.1.617.2, and AY.1 variants have several substitutions in the receptor binding domain (RBD), including L452R+E484Q, L452R+T478K, and K417N+L452R+T478K, respectively, that could potentially reduce effectiveness of therapeutic antibodies and current vaccines. Here we compared B.1.617 variants, and their single and double RBD substitutions for resistance to neutralization by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. Pseudoviruses with the B.1.617.1, B.1.617.2, and AY.1 spike showed a modest 1.5 to 4.4-fold reduction in neutralization titer by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for pseudoviruses with C.37, P.1, R.1, and B.1.526 spikes, but seven- and sixteen-fold reduction for vaccine-elicited and convalescent sera, respectively, was seen for pseudoviruses with the B.1.351 spike. Four of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses due to the L452R substitution, whereas six of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.1 pseudoviruses due to either the E484Q or L452R substitution. Against AY.1 pseudoviruses, the L452R and K417N substitutions accounted for the loss of neutralization by four antibodies and one antibody, respectively, whereas one antibody lost potency that could not be fully accounted for by a single RBD substitution. The modest resistance of B.1.617 variants to vaccine-elicited sera suggest that current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants, but the therapeutic antibodies need to be carefully selected based on their resistance profiles. Finally, the spike proteins of B.1.617 variants are more efficiently cleaved due to the P681R substitution, and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.
Neerukonda Sabari Nath、Vassell Russell、Echegaray Fernando、Erlandson Karl J.、Weiss Carol D.、Wang Richard、Bentley Lisa、Eakin Ann E.、Wang Wei、Katzelnick Leah C.、Lusvarghi Sabrina
Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthInfluenza and Emerging Infectious Diseases Division, Biomedical Advanced Research and Development Authority, U.S. Department of Health and Human ServicesDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationOffice of the Assistance Secretary for Preparedness and Response, Department of Health and Human ServicesDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of HealthDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug AdministrationViral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
基础医学生物科学研究方法、生物科学研究技术微生物学
SARS-CoV-2B.1.617 variantsneutralizing antibodiesneutralization resistancespike cleavagesyncytia formationantigenic distance
Neerukonda Sabari Nath,Vassell Russell,Echegaray Fernando,Erlandson Karl J.,Weiss Carol D.,Wang Richard,Bentley Lisa,Eakin Ann E.,Wang Wei,Katzelnick Leah C.,Lusvarghi Sabrina.SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.11.05.467523.点此复制
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