Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination

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Abstract

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19 vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2) and Omicron BA.1.1 in the BAL compared to COVID-19 convalescents, despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses, not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during re-infection, but offer limited protection against breakthrough infection, especially by Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by Omicron sublineage and future VOCs.

Abstract

COVID-19 mRNA vaccines induce poor anti-Omicron mucosal immunity, but this immunity can boosted with an intranasal immunization.

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Most cited references 61

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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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Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Delphine Planas, David Veyer, Artem Baidaliuk … (2021)

The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1-5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2-also termed the Delta variant-is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein.

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SARS-CoV-2 vaccines in development

Florian Krammer (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.

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Author and article information

Contributors

Jinyi Tang:

ORCID: https://orcid.org/0000-0003-3593-4324

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

Cong Zeng:

ORCID: https://orcid.org/0000-0003-4423-3634

Role: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing - review & editing

Thomas M. Cox: Role: Project administrationRole: Resources

Chaofan Li:

ORCID: https://orcid.org/0000-0002-5426-1498

Role: ConceptualizationRole: Data curationRole: InvestigationRole: Methodology

Young Min Son:

ORCID: https://orcid.org/0000-0003-2978-8703

Role: InvestigationRole: ResourcesRole: Validation

In Su Cheon:

ORCID: https://orcid.org/0000-0001-5160-7783

Role: InvestigationRole: ResourcesRole: Writing - review & editing

Yue Wu:

ORCID: https://orcid.org/0000-0003-3667-2960

Role: Project administrationRole: Validation

Supriya Behl: Role: InvestigationRole: Resources

Justin J. Taylor:

ORCID: https://orcid.org/0000-0001-9718-2901

Role: Resources

Rana Chakraborty:

ORCID: https://orcid.org/0000-0002-6585-0087

Role: ConceptualizationRole: SupervisionRole: Writing - original draft

Aaron J. Johnson:

ORCID: https://orcid.org/0000-0002-7921-484X

Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: Validation

Dante N. Schiavo:

ORCID: https://orcid.org/0000-0002-5332-977X

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

James P. Utz: Role: ConceptualizationRole: Writing - review & editing

Janani S. Reisenauer:

ORCID: https://orcid.org/0000-0002-8824-6691

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

David E. Midthun:

ORCID: https://orcid.org/0000-0002-4876-059X

Role: InvestigationRole: ResourcesRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

John J. Mullon: Role: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation

Eric S. Edell: Role: InvestigationRole: Resources

Mohamad G. Alameh: Role: MethodologyRole: ResourcesRole: ValidationRole: Writing - review & editing

Larry Borish: Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

William G. Teague: Role: Writing - review & editing

Mark H. Kaplan:

ORCID: https://orcid.org/0000-0002-2923-8245

Role: Funding acquisitionRole: Writing - review & editing

Drew Weissman:

ORCID: https://orcid.org/0000-0002-1501-6510

Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision

Ryan Kern:

ORCID: https://orcid.org/0000-0002-6311-2881

Role: ConceptualizationRole: InvestigationRole: Methodology

Haitao Hu:

ORCID: https://orcid.org/0000-0002-6964-2314

Role: MethodologyRole: ResourcesRole: Writing - review & editing

Robert Vassallo:

ORCID: https://orcid.org/0000-0003-2328-0255

Role: ConceptualizationRole: InvestigationRole: Writing - review & editing

Shan-Lu Liu: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Jie Sun:

ORCID: https://orcid.org/0000-0002-2347-4511

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

Journal

Journal ID (nlm-ta): Sci Immunol

Journal ID (iso-abbrev): Sci Immunol

Journal ID (publisher-id): sciimmunol

Journal ID (hwp): immunology

Title: Science Immunology

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2470-9468

Publication date (Electronic, pub): 19 July 2022

Publication date PMC-release: 19 July 2022

Electronic Location Identifier: eadd4853

Affiliations

[ ¹ ]Carter Immunology Center, University of Virginia, Charlottesville, VA, USA 22908

[ ² ]Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, USA 22908

[ ³ ]Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA 55905

[ ⁴ ]Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA 43210

[ ⁵ ]Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA 43210

[ ⁶ ]Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi-do, Republic of Korea 17546

[ ⁷ ]Department of Immunology, Mayo Clinic, Rochester, MN, USA 55905

[ ⁸ ]Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA 55905

[ ⁹ ]Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 98109

[ ¹⁰ ]Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA 19104

[ ¹¹ ]Division of Asthma, Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA 22908

[ ¹² ]Child Health Research Center, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA 22908

[ ¹³ ]Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA 46074

[ ¹⁴ ]Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA 77555

Author notes

[*]

These authors contribute equally

[#]

These authors contribute equally

[† ]Corresponding author. Email: liu.6244@ 123456osu.edu , js6re@ 123456virginia.edu

Author information

Jinyi Tang https://orcid.org/0000-0003-3593-4324

Cong Zeng https://orcid.org/0000-0003-4423-3634

Chaofan Li https://orcid.org/0000-0002-5426-1498

Young Min Son https://orcid.org/0000-0003-2978-8703

In Su Cheon https://orcid.org/0000-0001-5160-7783

Yue Wu https://orcid.org/0000-0003-3667-2960

Justin J. Taylor https://orcid.org/0000-0001-9718-2901

Rana Chakraborty https://orcid.org/0000-0002-6585-0087

Aaron J. Johnson https://orcid.org/0000-0002-7921-484X

Dante N. Schiavo https://orcid.org/0000-0002-5332-977X

Janani S. Reisenauer https://orcid.org/0000-0002-8824-6691

David E. Midthun https://orcid.org/0000-0002-4876-059X

Mark H. Kaplan https://orcid.org/0000-0002-2923-8245

Drew Weissman https://orcid.org/0000-0002-1501-6510

Ryan Kern https://orcid.org/0000-0002-6311-2881

Haitao Hu https://orcid.org/0000-0002-6964-2314

Robert Vassallo https://orcid.org/0000-0003-2328-0255

Jie Sun https://orcid.org/0000-0002-2347-4511

Article

Publisher ID: add4853

DOI: 10.1126/sciimmunol.add4853

PMC ID: 9348751

PubMed ID: 35857583

SO-VID: c3dc8ddd-2fd2-443a-bf8b-3fe6aea8e9d2

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 : 14 June 2022

Date accepted : 11 July 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: NIH R01 AI150473

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI057459

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI147903

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: AI157852

Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;

Award ID: NS122174

Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;

Award ID: NS103212

Funded by: FundRef http://dx.doi.org/10.13039/501100016206, Université de Sfax;

Award ID: AI147394

Funded by: FundRef http://dx.doi.org/10.13039/501100016206, Université de Sfax;

Award ID: AG047156

Funded by: FundRef http://dx.doi.org/10.13039/501100016206, Université de Sfax;

Award ID: AG069264

Funded by: FundRef http://dx.doi.org/10.13039/501100016206, Université de Sfax;

Award ID: AI147394S1

Funded by: FundRef , The Ohio State University;

Award ID: NCI U54CA260582

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Respiratory mucosal immunity against SARS-CoV-2 following mRNA vaccination

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Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 61

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

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

SARS-CoV-2 vaccines in development

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Cited by 116

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