Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

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Abstract

The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (T _FH) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG ⁺ B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.

Abstract

The SARS-CoV-2 Omicron variant possess many mutations within the receptor binding domain of the Spike protein, which confer increased transmissibility and higher antibody escape. Here, the authors carry out analysis of the serological and cellular immune responses of individuals with Omicron breakthrough infection.

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SARS-CoV-2 variants, spike mutations and immune escape

William T. Harvey, Alessandro M. Carabelli, Ben Jackson … (2021)

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

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An inflammatory cytokine signature predicts COVID-19 severity and survival

Diane Marie Del Valle, Seunghee Kim-Schulze, Hsin-Hui Huang … (2020)

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.

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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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Author and article information

Contributors

Hassen Kared:

ORCID: http://orcid.org/0000-0002-8220-997X

hassen.kared@medisin.uio.no

Ludvig A. Munthe:

ORCID: http://orcid.org/0000-0002-0344-3654

l.a.munthe@medisin.uio.no

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 18 July 2022

Publication date PMC-release: 18 July 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 4165

Affiliations

[1 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, KG Jebsen Centre for B cell malignancy, Institute of Clinical medicine, , University of Oslo, ; Oslo, Norway

[2 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Department of Immunology, , Oslo University Hospital, ; Oslo, Norway

[3 ]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Division of Infection Control, , Norwegian Institute of Public Health, ; Oslo, Norway

[4 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, ImmunoLingo Convergence Center, Institute of Clinical medicine, , University of Oslo, ; Oslo, Norway

[5 ]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Center for Fertility and Health, , Norwegian Institute of Public Health, ; Oslo, Norway

Author information

Hassen Kared http://orcid.org/0000-0002-8220-997X

Asia-Sophia Wolf http://orcid.org/0000-0003-1982-9487

Fridtjof Lund-Johansen http://orcid.org/0000-0002-2445-1258

Unni C. Nygaard http://orcid.org/0000-0002-2955-9970

Ludvig A. Munthe http://orcid.org/0000-0002-0344-3654

Article

Publisher ID: 31888

DOI: 10.1038/s41467-022-31888-y

PMC ID: 9293966

PubMed ID: 35851055

SO-VID: 511315ad-b254-46e1-9cd0-31a3ecec7c3c

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 22 January 2022

Date accepted : 8 July 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100005416, Norges Forskningsråd (Research Council of Norway);

Award ID: 312693

Award Recipient : Ludvig A. Munthe

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ScienceOpen disciplines: Uncategorized

Keywords: sars-cov-2,viral host response,viral infection

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ScienceOpen disciplines: Uncategorized

Keywords: sars-cov-2, viral host response, viral infection

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Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

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Novel Coronavirus Disease COVID-19

Most cited references 61

SARS-CoV-2 variants, spike mutations and immune escape

An inflammatory cytokine signature predicts COVID-19 severity and survival

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

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