Dissecting humoral immune responses to an MVA-vectored MERS-CoV vaccine in humans using a systems serology approach

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Summary

Besides neutralizing antibodies, which are considered an important measure for vaccine immunogenicity, Fc-mediated antibody functions can contribute to antibody-mediated protection. They are strongly influenced by structural antibody properties such as subclass and Fc glycan composition. We here applied a systems serology approach to dissect humoral immune responses induced by MVA-MERS-S, an MVA-vectored vaccine against the Middle East respiratory syndrome coronavirus (MERS-CoV). Building on preceding studies reporting the safety and immunogenicity of MVA-MERS-S, our study highlights the potential of a late boost, administered one year after prime, to enhance both neutralizing and Fc-mediated antibody functionality compared to the primary vaccination series. Distinct characteristics were observed for antibodies specific to the MERS-CoV spike protein S1 and S2 subunits, regarding subclass and glycan compositions as well as Fc functionality. These findings highlight the benefit of a late homologous booster vaccination with MVA-MERS-S and may be of interest for the design of future coronavirus vaccines.

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Highlights

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MVA-MERS-S vaccination induces antibodies with neutralizing and Fc functionality
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A late booster vaccination enhances both titers and functionality of antibodies
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S1- and S2-specific IgG differ in Fc functionality and N-linked glycan composition

Abstract

Cell biology; Immune response; Immunology; Virology

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Most cited references 91

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Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)

A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

David Khoury, Deborah Cromer, Arnold Reynaldi … (2021)

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

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Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology

Luca Piccoli, Young-Jun Park, M. Alejandra Tortorici … (2020)

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.

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Author and article information

Contributors

Leonie M. Weskamm

Journal

Journal ID (nlm-ta): iScience

Journal ID (iso-abbrev): iScience

Title: iScience

Publisher: Elsevier

ISSN (Electronic): 2589-0042

Publication date PMC-release: 08 July 2024

Publication date Collection: 16 August 2024

Publication date (Electronic): 08 July 2024

Volume: 27

Issue: 8

Electronic Location Identifier: 110470

Affiliations

[1 ]Institute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[2 ]Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

[3 ]German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany

[4 ]Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[5 ]Glyco-HAM, a Cooperation of Universität Hamburg, Technology Platform Mass Spectrometry and University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[6 ]University of Bordeaux, INSERM, INRIA, BPH, U1219, Sistm, Bordeaux, France

[7 ]Vaccine Research Institute, Creteil, France

[8 ]Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands

[9 ]Antibiotic Stewardship Team, Pharmacy of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[10 ]Institute of Virology, Philipps University Marburg, Marburg, Germany

[11 ]German Center for Infection Research, Partner Site Gießen-Marburg-Langen, Marburg, Germany

[12 ]Division of Virology, Department of Veterinary Sciences, Ludwig Maximilian University Munich, Munich, Germany

[13 ]German Center for Infection Research, Partner Site München, Munich, Germany

[14 ]CHU de Bordeaux, Service d’Information Médicale, Bordeaux, France

[15 ]Division of Infectious Diseases, 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Author notes

[∗ ]Corresponding author m.weskamm@ 123456uke.de

[16]

These authors contributed equally

[17]

Lead contact

Article

Publisher Item ID: S2589-0042(24)01695-X Publisher ID: 110470

DOI: 10.1016/j.isci.2024.110470

PMC ID: 11325358

PubMed ID: 39148710

SO-VID: 0c391934-3a40-4c45-ba90-1a67137608d4

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 11 November 2023

Date revision received : 11 June 2024

Date accepted : 3 July 2024

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Dissecting humoral immune responses to an MVA-vectored MERS-CoV vaccine in humans using a systems serology approach

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Summary

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Abstract

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European Journal of Microbiology and Immunology

Most cited references 91

Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology

Author and article information

Contributors

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Author notes

Article

History

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