학술논문
The Receptor Binding Domain of SARS-CoV-2 Lambda Variant Has a Better Chance Than the Delta Variant in Evading BNT162b2 COVID-19 mRNA Vaccine-Induced Humoral Immunity.
Document Type
Academic Journal
Author
Liu H; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Wei P; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Aviszus K; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Zhang Q; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agriculture University, Beijing 100193, China.; Linderberger J; Department of Biochemistry and Molecular Genetics School of Medicine, Anschutz Medical Center, University of Colorado, Aurora, CO 80216, USA.; Yang J; Department of Medicine, National Jewish Health, Denver, CO 80206, USA.; Liu J; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agriculture University, Beijing 100193, China.; Chen Z; State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agriculture University, Beijing 100193, China.; Waheed H; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Reynoso L; Department of Pharmacy, National Jewish Health, Denver, CO 80206, USA.; Downey GP; Department of Medicine, National Jewish Health, Denver, CO 80206, USA.; Frankel SK; Department of Medicine, National Jewish Health, Denver, CO 80206, USA.; Kappler JW; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Department of Pharmacy, National Jewish Health, Denver, CO 80206, USA.; Marrack P; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Department of Pharmacy, National Jewish Health, Denver, CO 80206, USA.; Zhang G; Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA.; Department of Pharmacy, National Jewish Health, Denver, CO 80206, USA.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
Abstract
The SARS-CoV-2 Delta and Lambda variants had been named variants of concern (VOC) and variants of interest (VOI), respectively, by the World Health Organization (WHO). Both variants have two mutations in the spike receptor binding domain (RBD) region, with L452R and T478K mutations in the Delta variant, and L452Q and F490S mutations in the Lambda variant. We used surface plasmon resonance (SPR)-based technology to evaluate the effect of these mutations on human angiotensin-converting enzyme 2 (ACE2) and Bamlanivimab binding. The affinity for the RBD ligand, ACE2, of the Delta RBD is approximately twice as strong as that of the wild type RBD, an increase that accounts for the increased infectivity of the Delta variant. On the other hand, in spite of its amino acid changes, the Lambda RBD has similar affinity to ACE2 as the wild type RBD. The protective anti-wild type RBD antibody Bamlanivimab binds very poorly to the Delta RBD and not at all to the Lambda RBD. Nevertheless, serum antibodies from individuals immunized with the BNT162b2 vaccine were found to bind well to the Delta RBD, but less efficiently to the Lambda RBD in contrast. As a result, the blocking ability of ACE2 binding by serum antibodies was decreased more by the Lambda than the Delta RBD. Titers of sera from BNT162b2 mRNA vaccinated individuals dropped 3-fold within six months of vaccination regardless of whether the target RBD was wild type, Delta or Lambda. This may account partially for the fall off with time in the protective effect of vaccines against any variant.