학술논문

Genome-Wide B Cell, CD4+, and CD8+ T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines
Document Type
article
Source
The Journal of Immunology. 206(11)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Immunology
Biodefense
Prevention
Immunization
Emerging Infectious Diseases
Biotechnology
Genetics
Infectious Diseases
Pneumonia & Influenza
Vaccine Related
Pneumonia
Lung
Human Genome
Aetiology
2.1 Biological and endogenous factors
Infection
Good Health and Well Being
Adult
Aged
Aged
80 and over
Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Epitopes
T-Lymphocyte
Female
Genome
Viral
Genome-Wide Association Study
Humans
Male
Middle Aged
Middle East Respiratory Syndrome Coronavirus
Severe acute respiratory syndrome-related coronavirus
SARS-CoV-2
Viral Vaccines
Biochemistry and cell biology
Language
Abstract
Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other global COVID pandemics will emerge in the coming years caused by yet another spillover of a bat-derived SARS-like coronavirus (SL-CoV) into humans. Determining the Ag and the human B cells, CD4+ and CD8+ T cell epitope landscapes that are conserved among human and animal coronaviruses should inform in the development of future pan-coronavirus vaccines. In the current study, using several immunoinformatics and sequence alignment approaches, we identified several human B cell and CD4+ and CD8+ T cell epitopes that are highly conserved in 1) greater than 81,000 SARS-CoV-2 genome sequences identified in 190 countries on six continents; 2) six circulating CoVs that caused previous human outbreaks of the common cold; 3) nine SL-CoVs isolated from bats; 4) nine SL-CoV isolated from pangolins; 5) three SL-CoVs isolated from civet cats; and 6) four MERS strains isolated from camels. Furthermore, the identified epitopes: 1) recalled B cells and CD4+ and CD8+ T cells from both COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2, and 2) induced strong B cell and T cell responses in humanized HLA-DR1/HLA-A*02:01 double-transgenic mice. The findings pave the way to develop a preemptive multiepitope pan-coronavirus vaccine to protect against past, current, and future outbreaks.