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Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; wit...

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Autores principales: Prakash, Swayam, Dhanushkodi, Nisha R., Zayou, Latifa, Ibraim, Izabela Coimbra, Quadiri, Afshana, Coulon, Pierre Gregoire, Tifrea, Delia F, Suzler, Berfin, Amin, Mohamed, Chilukuri, Amruth, Edwards, Robert A, Vahed, Hawa, Nesburn, Anthony B, Kuppermann, Baruch D, Ulmer, Jeffrey B., Gil, Daniel, Jones, Trevor M., BenMohamed, Lbachir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245830/
https://www.ncbi.nlm.nih.gov/pubmed/37292861
http://dx.doi.org/10.1101/2023.05.24.541850
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author Prakash, Swayam
Dhanushkodi, Nisha R.
Zayou, Latifa
Ibraim, Izabela Coimbra
Quadiri, Afshana
Coulon, Pierre Gregoire
Tifrea, Delia F
Suzler, Berfin
Amin, Mohamed
Chilukuri, Amruth
Edwards, Robert A
Vahed, Hawa
Nesburn, Anthony B
Kuppermann, Baruch D
Ulmer, Jeffrey B.
Gil, Daniel
Jones, Trevor M.
BenMohamed, Lbachir
author_facet Prakash, Swayam
Dhanushkodi, Nisha R.
Zayou, Latifa
Ibraim, Izabela Coimbra
Quadiri, Afshana
Coulon, Pierre Gregoire
Tifrea, Delia F
Suzler, Berfin
Amin, Mohamed
Chilukuri, Amruth
Edwards, Robert A
Vahed, Hawa
Nesburn, Anthony B
Kuppermann, Baruch D
Ulmer, Jeffrey B.
Gil, Daniel
Jones, Trevor M.
BenMohamed, Lbachir
author_sort Prakash, Swayam
collection PubMed
description BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; with the mortality rate still surpassing even the worst mortality rates recorded for the influenza viruses. The continuous emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, have prolonged the COVID-19 pandemic and outlines the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. METHODS: In the present study, we designed a multi-epitope-based Coronavirus vaccine that incorporated B, CD4(+), and CD8(+) T cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8(+) and CD4(+) T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-Coronavirus vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. RESULTS: The Pan-Coronavirus vaccine: (i) is safe; (ii) induces high frequencies of lung-resident functional CD8(+) and CD4(+) T(EM) and T(RM) cells; and (iii) provides robust protection against virus replication and COVID-19-related lung pathology and death caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2) and Omicron (B.1.1.529). CONCLUSIONS: A multi-epitope pan-Coronavirus vaccine bearing conserved human B and T cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that cleared the virus, and reduced COVID-19-related lung pathology and death caused by multiple SARS-CoV-2 VOCs.
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spelling pubmed-102458302023-06-08 Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern Prakash, Swayam Dhanushkodi, Nisha R. Zayou, Latifa Ibraim, Izabela Coimbra Quadiri, Afshana Coulon, Pierre Gregoire Tifrea, Delia F Suzler, Berfin Amin, Mohamed Chilukuri, Amruth Edwards, Robert A Vahed, Hawa Nesburn, Anthony B Kuppermann, Baruch D Ulmer, Jeffrey B. Gil, Daniel Jones, Trevor M. BenMohamed, Lbachir bioRxiv Article BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; with the mortality rate still surpassing even the worst mortality rates recorded for the influenza viruses. The continuous emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, have prolonged the COVID-19 pandemic and outlines the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. METHODS: In the present study, we designed a multi-epitope-based Coronavirus vaccine that incorporated B, CD4(+), and CD8(+) T cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8(+) and CD4(+) T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-Coronavirus vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. RESULTS: The Pan-Coronavirus vaccine: (i) is safe; (ii) induces high frequencies of lung-resident functional CD8(+) and CD4(+) T(EM) and T(RM) cells; and (iii) provides robust protection against virus replication and COVID-19-related lung pathology and death caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2) and Omicron (B.1.1.529). CONCLUSIONS: A multi-epitope pan-Coronavirus vaccine bearing conserved human B and T cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that cleared the virus, and reduced COVID-19-related lung pathology and death caused by multiple SARS-CoV-2 VOCs. Cold Spring Harbor Laboratory 2023-05-24 /pmc/articles/PMC10245830/ /pubmed/37292861 http://dx.doi.org/10.1101/2023.05.24.541850 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Prakash, Swayam
Dhanushkodi, Nisha R.
Zayou, Latifa
Ibraim, Izabela Coimbra
Quadiri, Afshana
Coulon, Pierre Gregoire
Tifrea, Delia F
Suzler, Berfin
Amin, Mohamed
Chilukuri, Amruth
Edwards, Robert A
Vahed, Hawa
Nesburn, Anthony B
Kuppermann, Baruch D
Ulmer, Jeffrey B.
Gil, Daniel
Jones, Trevor M.
BenMohamed, Lbachir
Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title_full Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title_fullStr Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title_full_unstemmed Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title_short Cross-Protection Induced by Highly Conserved Human B, CD4(+,) and CD8(+) T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern
title_sort cross-protection induced by highly conserved human b, cd4(+,) and cd8(+) t cell epitopes-based coronavirus vaccine against severe infection, disease, and death caused by multiple sars-cov-2 variants of concern
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245830/
https://www.ncbi.nlm.nih.gov/pubmed/37292861
http://dx.doi.org/10.1101/2023.05.24.541850
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