Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants wi...

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Main Authors: Dicle Yalcin, Sydney J. Bennett, Jared Sheehan, Amber J. Trauth, For Yue Tso, John T. West, Michael E. Hagensee, Alistair J. Ramsay, Charles Wood
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/8/7292
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author Dicle Yalcin
Sydney J. Bennett
Jared Sheehan
Amber J. Trauth
For Yue Tso
John T. West
Michael E. Hagensee
Alistair J. Ramsay
Charles Wood
author_facet Dicle Yalcin
Sydney J. Bennett
Jared Sheehan
Amber J. Trauth
For Yue Tso
John T. West
Michael E. Hagensee
Alistair J. Ramsay
Charles Wood
author_sort Dicle Yalcin
collection DOAJ
description The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery.
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spelling doaj.art-6f8f81ebe81340ac93c6a2fe25d1e9422023-11-17T19:38:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248729210.3390/ijms24087292Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial VaccinationsDicle Yalcin0Sydney J. Bennett1Jared Sheehan2Amber J. Trauth3For Yue Tso4John T. West5Michael E. Hagensee6Alistair J. Ramsay7Charles Wood8Department of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Microbiology, Immunology and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartments of Medicine, Section of Infectious Diseases, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartments of Medicine, Section of Infectious Diseases, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Microbiology, Immunology and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USAThe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery.https://www.mdpi.com/1422-0067/24/8/7292SARS-CoV-2mRNA vaccineVirScanPhIP-Seqspikeepitope map
spellingShingle Dicle Yalcin
Sydney J. Bennett
Jared Sheehan
Amber J. Trauth
For Yue Tso
John T. West
Michael E. Hagensee
Alistair J. Ramsay
Charles Wood
Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
International Journal of Molecular Sciences
SARS-CoV-2
mRNA vaccine
VirScan
PhIP-Seq
spike
epitope map
title Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
title_full Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
title_fullStr Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
title_full_unstemmed Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
title_short Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations
title_sort longitudinal variations in antibody responses against sars cov 2 spike epitopes upon serial vaccinations
topic SARS-CoV-2
mRNA vaccine
VirScan
PhIP-Seq
spike
epitope map
url https://www.mdpi.com/1422-0067/24/8/7292
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