Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants

The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the s...

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Main Authors: Laura Ballesteros-Sanabria, Hector F. Pelaez-Prestel, Alvaro Ras-Carmona, Pedro A. Reche
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/5/996
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author Laura Ballesteros-Sanabria
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Pedro A. Reche
author_facet Laura Ballesteros-Sanabria
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Pedro A. Reche
author_sort Laura Ballesteros-Sanabria
collection DOAJ
description The outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the spike glycoprotein, which is known to bind to the receptor angiotensin converting enzyme 2 (ACE2) in host cells via the receptor-binding domain (RBD). Antibodies binding to this domain can block the interaction with the receptor and prevent viral entry into the cells. Additionally, these vaccines can also induce spike-specific T cells which could contribute to providing protection against the virus. However, the emergence of new SARS-CoV-2 variants can impair the immunity generated by COVID-19 vaccines if mutations occur in cognate epitopes, precluding immune recognition. Here, we evaluated the chance of five SARS-CoV-2 variants of concern (VOCs), Alpha, Beta, Gamma, Delta and Omicron, to escape spike-specific immunity induced by vaccines. To that end, we examined the impact of the SARS-CoV-2 variant mutations on residues located on experimentally verified spike-specific epitopes, deposited at the Immune Epitope Database, that are targeted by neutralizing antibodies or recognized by T cells. We found about 300 of such B cell epitopes, which were largely overlapping, and could be grouped into 54 B cell epitope clusters sharing ≥ 7 residues. Most of the B cell epitope clusters map in the RBD domain (39 out of 54) and 20%, 50%, 37%, 44% and 57% of the total are mutated in SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants, respectively. We also found 234 experimentally verified CD8 and CD4 T cell epitopes that were distributed evenly throughout the spike protein. Interestingly, in each SARS-CoV-2 VOC, over 87% and 79% of CD8 and CD4 T cell epitopes, respectively, are not mutated. These observations suggest that SARS-CoV-2 VOCs—particularly the Omicron variant—may be prone to escape spike-specific antibody immunity, but not cellular immunity, elicited by COVID-19 vaccines.
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spelling doaj.art-3f48d461ae68481c98eba60b01cd08d82023-11-23T10:09:33ZengMDPI AGBiomedicines2227-90592022-04-0110599610.3390/biomedicines10050996Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 VariantsLaura Ballesteros-Sanabria0Hector F. Pelaez-Prestel1Alvaro Ras-Carmona2Pedro A. Reche3Laboratory of Immunomedicine, Department of Immunology & O2, School of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, S/N, 28040 Madrid, SpainLaboratory of Immunomedicine, Department of Immunology & O2, School of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, S/N, 28040 Madrid, SpainLaboratory of Immunomedicine, Department of Immunology & O2, School of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, S/N, 28040 Madrid, SpainLaboratory of Immunomedicine, Department of Immunology & O2, School of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, S/N, 28040 Madrid, SpainThe outbreak of SARS-CoV-2 leading to the declaration of the COVID-19 global pandemic has led to the urgent development and deployment of several COVID-19 vaccines. Many of these new vaccines, including those based on mRNA and adenoviruses, are aimed to generate neutralizing antibodies against the spike glycoprotein, which is known to bind to the receptor angiotensin converting enzyme 2 (ACE2) in host cells via the receptor-binding domain (RBD). Antibodies binding to this domain can block the interaction with the receptor and prevent viral entry into the cells. Additionally, these vaccines can also induce spike-specific T cells which could contribute to providing protection against the virus. However, the emergence of new SARS-CoV-2 variants can impair the immunity generated by COVID-19 vaccines if mutations occur in cognate epitopes, precluding immune recognition. Here, we evaluated the chance of five SARS-CoV-2 variants of concern (VOCs), Alpha, Beta, Gamma, Delta and Omicron, to escape spike-specific immunity induced by vaccines. To that end, we examined the impact of the SARS-CoV-2 variant mutations on residues located on experimentally verified spike-specific epitopes, deposited at the Immune Epitope Database, that are targeted by neutralizing antibodies or recognized by T cells. We found about 300 of such B cell epitopes, which were largely overlapping, and could be grouped into 54 B cell epitope clusters sharing ≥ 7 residues. Most of the B cell epitope clusters map in the RBD domain (39 out of 54) and 20%, 50%, 37%, 44% and 57% of the total are mutated in SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants, respectively. We also found 234 experimentally verified CD8 and CD4 T cell epitopes that were distributed evenly throughout the spike protein. Interestingly, in each SARS-CoV-2 VOC, over 87% and 79% of CD8 and CD4 T cell epitopes, respectively, are not mutated. These observations suggest that SARS-CoV-2 VOCs—particularly the Omicron variant—may be prone to escape spike-specific antibody immunity, but not cellular immunity, elicited by COVID-19 vaccines.https://www.mdpi.com/2227-9059/10/5/996SARS-CoV-2 variants of concernomicronCOVID-19 vaccinesimmune escapeneutralizing antibodiesB cell epitope
spellingShingle Laura Ballesteros-Sanabria
Hector F. Pelaez-Prestel
Alvaro Ras-Carmona
Pedro A. Reche
Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
Biomedicines
SARS-CoV-2 variants of concern
omicron
COVID-19 vaccines
immune escape
neutralizing antibodies
B cell epitope
title Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
title_full Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
title_fullStr Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
title_full_unstemmed Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
title_short Resilience of Spike-Specific Immunity Induced by COVID-19 Vaccines against SARS-CoV-2 Variants
title_sort resilience of spike specific immunity induced by covid 19 vaccines against sars cov 2 variants
topic SARS-CoV-2 variants of concern
omicron
COVID-19 vaccines
immune escape
neutralizing antibodies
B cell epitope
url https://www.mdpi.com/2227-9059/10/5/996
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