Cross-protection Induced by Highly Conserved Human B, CD4, and CD8 T-cell Epitopes-based Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Feb 6

PMID 38318166

Authors

Swayam Prakash

Nisha R Dhanushkodi

Latifa Zayou

Izabela Coimbra Ibraim

Afshana Quadiri

Pierre Gregoire Coulon

Delia F Tifrea

Berfin Suzer

Amin Mohammed Shaik

Amruth Chilukuri

Robert A Edwards

Mahmoud Singer

Hawa Vahed

Anthony B Nesburn

Baruch D Kuppermann

Jeffrey B Ulmer

Daniel Gil

Trevor M Jones

Lbachir BenMohamed

Affiliations

Soon will be listed here.

Abstract

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 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.

Methods: 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-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.

Results: The pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8 and CD4 T and T cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were 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).

Conclusion: A multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.

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