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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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