Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months after infection. Both BA.1 and BA.2 infections robustly boosted neutralization activity against the infecting strain while expanding breadth against BA.4, although neutralization activity was substantially reduced for the more recent XBB and BQ.1.1 strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modeling of neutralization titers predicts that protection from symptomatic reinfection against antigenically similar strains will be durable but is undermined by new emerging strains with further neutralization escape.

Abstract

Omicron breakthrough infection elicits durable neutralising activity by recalling cross-reactive vaccine-elicited memory B cells.

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Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

Victor M Corman, Olfert Landt, Marco Kaiser … (2020)

Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.

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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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Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

Ching-Lin Hsieh, Jory A Goldsmith, Jeffrey Schaub … (2020)

The COVID-19 pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. Here, we characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting ~10-fold higher expression than its parental construct and the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.

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Author and article information

Contributors

Wen Shi Lee:

ORCID: https://orcid.org/0000-0001-7285-4054

Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Hyon-Xhi Tan:

ORCID: https://orcid.org/0000-0003-1064-3934

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Arnold Reynaldi:

ORCID: https://orcid.org/0000-0002-5529-5542

Role: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: Visualization

Robyn Esterbauer:

ORCID: https://orcid.org/0000-0002-7091-0048

Role: Investigation

Marios Koutsakos:

ORCID: https://orcid.org/0000-0001-9994-9723

Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing - review & editing

Julie Nguyen:

ORCID: https://orcid.org/0000-0003-1100-1730

Role: Investigation

Thakshila Amarasena:

ORCID: https://orcid.org/0000-0003-4685-4127

Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation

Helen E. Kent: Role: Resources

Anupriya Aggarwal: Role: InvestigationRole: MethodologyRole: Resources

Stuart G. Turville:

ORCID: https://orcid.org/0000-0003-1918-5343

Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: Writing - review & editing

George Taiaroa:

ORCID: https://orcid.org/0009-0009-3050-1424

Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Resources

Paul Kinsella:

ORCID: https://orcid.org/0000-0002-6167-9366

Role: Investigation

Kwee Chin Liew:

ORCID: https://orcid.org/0000-0002-4692-2479

Role: Resources

Thomas Tran: Role: Investigation

Deborah A. Williamson:

ORCID: https://orcid.org/0000-0001-7363-6665

Role: InvestigationRole: ResourcesRole: ValidationRole: Writing - review & editing

Deborah Cromer:

ORCID: https://orcid.org/0000-0002-5276-5094

Role: ConceptualizationRole: Formal analysisRole: SoftwareRole: SupervisionRole: Writing - review & editing

Miles P. Davenport:

ORCID: https://orcid.org/0000-0002-4751-1831

Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing - review & editing

Stephen J. Kent:

ORCID: https://orcid.org/0000-0002-8539-4891

Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing - review & editing

Jennifer A. Juno:

ORCID: https://orcid.org/0000-0002-9072-1017

Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: ResourcesRole: Supervision

David S. Khoury: Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ResourcesRole: ValidationRole: Visualization

Adam K. Wheatley:

ORCID: https://orcid.org/0000-0002-5593-9387

Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing - original draftRole: Writing - review & editing

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): sciadv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: July 2023

Publication date (Electronic, pub): 21 July 2023

Volume: 9

Issue: 29

Electronic Location Identifier: eadg5301

Affiliations

[ ¹ ]Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

[ ² ]Kirby Institute, University of New South Wales, Kensington, NSW, Australia.

[ ³ ]Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

[ ⁴ ]Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

[ ⁵ ]Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia.

Author notes

[* ]Corresponding author. Email: a.wheatley@ 123456unimelb.edu.au

[†]

These authors contributed equally to this work.

Author information

Wen Shi Lee https://orcid.org/0000-0001-7285-4054

Hyon-Xhi Tan https://orcid.org/0000-0003-1064-3934

Arnold Reynaldi https://orcid.org/0000-0002-5529-5542

Robyn Esterbauer https://orcid.org/0000-0002-7091-0048

Marios Koutsakos https://orcid.org/0000-0001-9994-9723

Julie Nguyen https://orcid.org/0000-0003-1100-1730

Thakshila Amarasena https://orcid.org/0000-0003-4685-4127

Stuart G. Turville https://orcid.org/0000-0003-1918-5343

George Taiaroa https://orcid.org/0009-0009-3050-1424

Paul Kinsella https://orcid.org/0000-0002-6167-9366

Kwee Chin Liew https://orcid.org/0000-0002-4692-2479

Deborah A. Williamson https://orcid.org/0000-0001-7363-6665

Deborah Cromer https://orcid.org/0000-0002-5276-5094

Miles P. Davenport https://orcid.org/0000-0002-4751-1831

Stephen J. Kent https://orcid.org/0000-0002-8539-4891

Jennifer A. Juno https://orcid.org/0000-0002-9072-1017

Adam K. Wheatley https://orcid.org/0000-0002-5593-9387

Article

Publisher ID: adg5301

DOI: 10.1126/sciadv.adg5301

PMC ID: 10361595

PubMed ID: 37478181

SO-VID: 669841a8-1ab4-4121-8542-d36f42e66721

Copyright © Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 03 January 2023

Date accepted : 21 June 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;

Award ID: 1149990

Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;

Award ID: 1162760

Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;

Award ID: 2004398

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Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

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Novel Coronavirus Disease COVID-19

Most cited references 30

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

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

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

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Cited by 5

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