Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort

Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and...

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Main Authors: Jared Sheehan, Amber J. Trauth, Michael E. Hagensee, Alistair J. Ramsay
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/1/44
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author Jared Sheehan
Amber J. Trauth
Michael E. Hagensee
Alistair J. Ramsay
author_facet Jared Sheehan
Amber J. Trauth
Michael E. Hagensee
Alistair J. Ramsay
author_sort Jared Sheehan
collection DOAJ
description Vaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive IgG and IgA Ab responses did not decline significantly through 9 months post-diagnosis. These responses improved significantly following vaccination and remained elevated through at least 12-months. SARS-CoV-2 neutralizing Ab activity was detected in convalescent sera through 9 months post-diagnosis, although it trended downwards from 3 months. Neutralizing Ab activity against the Wuhan-Hu-1 strain was significantly improved by vaccination, to levels that persisted through the end of the study. However, sera collected from vaccinated convalescent subjects also had significant neutralization activity against Delta B.1.617.2 and Omicron variants that persisted for at least 2–3 months, unlike sera from unvaccinated convalescent controls. Thus, vaccination of Wuhan-Hu-1–convalescent individuals with the BNT162b2 vaccine improved and sustained protective neutralizing Ab activity against SARS-CoV-2, including cross-reactive neutralizing activity against variants that emerged months later.
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spelling doaj-art-d832738617d642299f855cd6543416e02025-01-24T13:44:42ZengMDPI AGPathogens2076-08172025-01-011414410.3390/pathogens14010044Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent CohortJared Sheehan0Amber J. Trauth1Michael E. Hagensee2Alistair J. Ramsay3Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USAStanley S. Scott Cancer, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USADepartment of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USAVaccination of COVID-19–convalescent individuals may generate ‘hybrid’ immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1–based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD–specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive IgG and IgA Ab responses did not decline significantly through 9 months post-diagnosis. These responses improved significantly following vaccination and remained elevated through at least 12-months. SARS-CoV-2 neutralizing Ab activity was detected in convalescent sera through 9 months post-diagnosis, although it trended downwards from 3 months. Neutralizing Ab activity against the Wuhan-Hu-1 strain was significantly improved by vaccination, to levels that persisted through the end of the study. However, sera collected from vaccinated convalescent subjects also had significant neutralization activity against Delta B.1.617.2 and Omicron variants that persisted for at least 2–3 months, unlike sera from unvaccinated convalescent controls. Thus, vaccination of Wuhan-Hu-1–convalescent individuals with the BNT162b2 vaccine improved and sustained protective neutralizing Ab activity against SARS-CoV-2, including cross-reactive neutralizing activity against variants that emerged months later.https://www.mdpi.com/2076-0817/14/1/44COVID-19BNT162b2 vaccinehybrid immunityconvalescent serum IgG and IgA antibodiesserum SARS-CoV-2 neutralizing antibodies
spellingShingle Jared Sheehan
Amber J. Trauth
Michael E. Hagensee
Alistair J. Ramsay
Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
Pathogens
COVID-19
BNT162b2 vaccine
hybrid immunity
convalescent serum IgG and IgA antibodies
serum SARS-CoV-2 neutralizing antibodies
title Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
title_full Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
title_fullStr Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
title_full_unstemmed Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
title_short Characterization of Vaccine-Enhanced Humoral Immune Responses Against Emergent SARS-CoV-2 Variants in a Convalescent Cohort
title_sort characterization of vaccine enhanced humoral immune responses against emergent sars cov 2 variants in a convalescent cohort
topic COVID-19
BNT162b2 vaccine
hybrid immunity
convalescent serum IgG and IgA antibodies
serum SARS-CoV-2 neutralizing antibodies
url https://www.mdpi.com/2076-0817/14/1/44
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