Divergent SARS CoV-2 Omicron-reactive T- and B cell responses in COVID-19 vaccine recipients

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Abstract

The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses targeting SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays with infectious virus showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent (up to a 34-fold decrease compared to WT). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV.2 priming partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to WT. SARS-CoV-2-specific T-cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4+ than CD8+ T-cells. No significant differences were detected between WT- and variant-specific CD4+ or CD8+ T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations are needed to further restore Omicron cross-neutralization by antibodies.

Abstract

Vaccination-induced SARS-CoV-2-specific CD4+ and CD8+ T-cells targeting the ancestral Spike protein cross-recognize the Omicron variant.

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Most cited references 53

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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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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Author and article information

Contributors

Corine H. GeurtsvanKessel:

ORCID: https://orcid.org/0000-0002-7678-314X

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

Daryl Geers:

ORCID: https://orcid.org/0000-0002-3432-0761

Role: InvestigationRole: MethodologyRole: ValidationRole: Visualization

Katharina S. Schmitz:

ORCID: https://orcid.org/0000-0002-8537-0646

Role: InvestigationRole: Project administrationRole: Resources

Anna Z. Mykytyn:

ORCID: https://orcid.org/0000-0001-7188-6871

Role: Methodology

Mart M Lamers:

ORCID: https://orcid.org/0000-0002-1431-4022

Role: Formal analysisRole: InvestigationRole: MethodologyRole: Resources

Susanne Bogers:

ORCID: https://orcid.org/0000-0002-8212-2946

Role: Data curationRole: Investigation

Sandra Scherbeijn: Role: InvestigationRole: MethodologyRole: SupervisionRole: Validation

Lennert Gommers:

ORCID: https://orcid.org/0000-0002-4542-0303

Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing - review & editing

Roos S.G. Sablerolles:

ORCID: https://orcid.org/0000-0002-6647-6584

Role: Data curationRole: InvestigationRole: Resources

Nella N. Nieuwkoop: Role: Investigation

Laurine C. Rijsbergen:

ORCID: https://orcid.org/0000-0001-8328-2899

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

Laura L.A. van Dijk:

ORCID: https://orcid.org/0000-0001-5716-2738

Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing - review & editing

Janet de Wilde: Role: Investigation

Kimberley Alblas:

ORCID: https://orcid.org/0000-0001-7815-3806

Role: Investigation

Tim I. Breugem: Role: Investigation

Bart J.A. Rijnders:

ORCID: https://orcid.org/0000-0003-3343-9610

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

Herbert de Jager:

ORCID: https://orcid.org/0000-0001-7516-6054

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

Daniela Weiskopf:

ORCID: https://orcid.org/0000-0003-2968-7371

Role: Funding acquisitionRole: Resources

P. Hugo M. van der Kuy:

ORCID: https://orcid.org/0000-0002-7128-8801

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing - review & editing

Alessandro Sette:

ORCID: https://orcid.org/0000-0001-7013-2250

Role: Funding acquisitionRole: Resources

Marion P.G. Koopmans:

ORCID: https://orcid.org/0000-0002-5204-2312

Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing - review & editing

Alba Grifoni:

ORCID: https://orcid.org/0000-0002-2209-5966

Role: Formal analysisRole: MethodologyRole: Resources

Bart L. Haagmans:

ORCID: https://orcid.org/0000-0001-6221-2015

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

Rory D. de Vries:

ORCID: https://orcid.org/0000-0003-2817-0127

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: 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): 03 February 2022

Publication date PMC-release: 03 February 2022

Electronic Location Identifier: eabo2202

Affiliations

[ ¹ ]Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands

[ ² ]Department of Hospital Pharmacy, Erasmus MC, Rotterdam, Netherlands

[ ³ ]Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, Netherlands

[ ⁴ ]Department of Occupational Health Services, Erasmus MC, Rotterdam, Netherlands

[ ⁵ ]Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA

[ ⁶ ]Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.

Author notes

[† ]

Authors contributed equally

[$ ]

Authors contributed equally

[* ] Corresponding authors: Corine H. GeurtsvanKessel ( c.geurtsvankessel@ 123456erasmusmc.nl ), Bart L. Haagmans ( b.haagmans@ 123456erasmusmc.nl ) and Rory D. de Vries ( r.d.devries@ 123456erasmusmc.nl ).

Author information

Corine H. GeurtsvanKessel https://orcid.org/0000-0002-7678-314X

Daryl Geers https://orcid.org/0000-0002-3432-0761

Katharina S. Schmitz https://orcid.org/0000-0002-8537-0646

Anna Z. Mykytyn https://orcid.org/0000-0001-7188-6871

Mart M Lamers https://orcid.org/0000-0002-1431-4022

Susanne Bogers https://orcid.org/0000-0002-8212-2946

Lennert Gommers https://orcid.org/0000-0002-4542-0303

Roos S.G. Sablerolles https://orcid.org/0000-0002-6647-6584

Laurine C. Rijsbergen https://orcid.org/0000-0001-8328-2899

Laura L.A. van Dijk https://orcid.org/0000-0001-5716-2738

Kimberley Alblas https://orcid.org/0000-0001-7815-3806

Bart J.A. Rijnders https://orcid.org/0000-0003-3343-9610

Herbert de Jager https://orcid.org/0000-0001-7516-6054

Daniela Weiskopf https://orcid.org/0000-0003-2968-7371

P. Hugo M. van der Kuy https://orcid.org/0000-0002-7128-8801

Alessandro Sette https://orcid.org/0000-0001-7013-2250

Marion P.G. Koopmans https://orcid.org/0000-0002-5204-2312

Alba Grifoni https://orcid.org/0000-0002-2209-5966

Bart L. Haagmans https://orcid.org/0000-0001-6221-2015

Rory D. de Vries https://orcid.org/0000-0003-2817-0127

Article

Publisher ID: abo2202

DOI: 10.1126/sciimmunol.abo2202

PMC ID: 8939771

PubMed ID: 35113647

SO-VID: 9bbc084c-85da-41cc-abf1-278347c2cbc7

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 : 20 January 2022

Date accepted : 31 January 2022

Funding

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

Award ID: 75N93021C00016

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

Award ID: 75N9301900065

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

Award ID: 75N9301900065

Funded by: FundRef http://dx.doi.org/10.13039/100010661, Horizon 2020 Framework Programme;

Award ID: 101003589

Funded by: FundRef , ZonMW;

Award ID: 10150062010008

Funded by: FundRef , ZonMW;

Award ID: 10430072110001

Funded by: FundRef , ZonMW;

Award ID: 10430072110001

Funded by: FundRef , Health Holland;

Award ID: EMCLHS20017

Funded by: FundRef , ZonMW;

Award ID: 10430072110001

Funded by: FundRef , ZonMW;

Award ID: 10430072110001

Funded by: FundRef , Health Holland;

Award ID: EMCLHS20017

Funded by: FundRef , Health Holland;

Award ID: EMCLHS20017

Funded by: FundRef , Health Holland;

Award ID: LSHM19136

Funded by: FundRef , NIH/NIAID CEIRR;

Award ID: 75N93021C00014

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Divergent SARS CoV-2 Omicron-reactive T- and B cell responses in COVID-19 vaccine recipients

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Novel Coronavirus Disease COVID-19

Most cited references 53

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

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

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Cited by 187

Most referenced authors 2,712