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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
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 vari...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569855/ https://www.ncbi.nlm.nih.gov/pubmed/36232627 http://dx.doi.org/10.3390/ijms231911325 |
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author | Liu, Haolin Wei, Pengcheng Aviszus, Katja Zhang, Qianqian Linderberger, Jared Yang, John Liu, Junfeng Chen, Zhongzhou Waheed, Hassan Reynoso, Lyndon Downey, Gregory P. Frankel, Stephen K. Kappler, John W. Marrack, Philippa Zhang, Gongyi |
author_facet | Liu, Haolin Wei, Pengcheng Aviszus, Katja Zhang, Qianqian Linderberger, Jared Yang, John Liu, Junfeng Chen, Zhongzhou Waheed, Hassan Reynoso, Lyndon Downey, Gregory P. Frankel, Stephen K. Kappler, John W. Marrack, Philippa Zhang, Gongyi |
author_sort | Liu, Haolin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9569855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95698552022-10-17 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 Liu, Haolin Wei, Pengcheng Aviszus, Katja Zhang, Qianqian Linderberger, Jared Yang, John Liu, Junfeng Chen, Zhongzhou Waheed, Hassan Reynoso, Lyndon Downey, Gregory P. Frankel, Stephen K. Kappler, John W. Marrack, Philippa Zhang, Gongyi Int J Mol Sci Communication 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. MDPI 2022-09-26 /pmc/articles/PMC9569855/ /pubmed/36232627 http://dx.doi.org/10.3390/ijms231911325 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Liu, Haolin Wei, Pengcheng Aviszus, Katja Zhang, Qianqian Linderberger, Jared Yang, John Liu, Junfeng Chen, Zhongzhou Waheed, Hassan Reynoso, Lyndon Downey, Gregory P. Frankel, Stephen K. Kappler, John W. Marrack, Philippa Zhang, Gongyi 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569855/ https://www.ncbi.nlm.nih.gov/pubmed/36232627 http://dx.doi.org/10.3390/ijms231911325 |
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