Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

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Abstract

SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.

Abstract

Here, the authors characterize the antibody response from vaccinated (Pfizer BNT-162b2), infected and uninfected individuals against emerging variants of concern of SARS-CoV-2, finding reduced neutralization of a South African isolate. High IgG titers in the saliva of vaccinees suggest that transmission may be reduced.

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Most cited references 46

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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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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Author and article information

Contributors

Ulrich Rothbauer:

ORCID: http://orcid.org/0000-0001-5923-8986

Ulrich.rothbauer@nmi.de

Michael Schindler:

ORCID: http://orcid.org/0000-0001-8989-5813

Michael.Schindler@med.uni-tuebingen.de

Nicole Schneiderhan-Marra:

ORCID: http://orcid.org/0000-0001-6785-181X

Nicole.schneiderhan@nmi.de

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): 25 May 2021

Publication date PMC-release: 25 May 2021

Publication date Collection: 2021

Volume: 12

Electronic Location Identifier: 3109

Affiliations

[1 ]GRID grid.461765.7, ISNI 0000 0000 9457 1306, NMI Natural and Medical Sciences Institute at the University of Tübingen, ; Reutlingen, Germany

[2 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Institute for Medical Virology and Epidemiology, , University Hospital Tübingen, ; Tübingen, Germany

[3 ]GRID grid.10392.39, ISNI 0000 0001 2190 1447, Institute of Tropical Medicine, , University of Tübingen, ; Tübingen, Germany

[4 ]GRID grid.10392.39, ISNI 0000 0001 2190 1447, Pharmaceutical Biotechnology, , University of Tübingen, ; Tübingen, Germany

[5 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Anaesthesiology and Intensive Care Medicine, , University Hospital Tübingen, ; Tübingen, Germany

[6 ]GRID grid.452463.2, German Center for Infection Research (DZIF), , partner site Tübingen, ; Tübingen, Germany

[7 ]Signatope GmbH, Reutlingen, Germany

[8 ]GRID grid.10392.39, ISNI 0000 0001 2190 1447, Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, , University of Tübingen, ; Tübingen, Germany

[9 ]GRID grid.10392.39, ISNI 0000 0001 2190 1447, Department of Women’s Health, Research Institute for Women’s Health, , University of Tübingen, ; Tübingen, Germany

[10 ]GRID grid.19006.3e, ISNI 0000 0000 9632 6718, Department of Medicine/Cardiology, Cardiovascular Research Laboratories, , David Geffen School of Medicine at UCLA, ; Los Angeles, USA

[11 ]GRID grid.7490.a, ISNI 0000 0001 2238 295X, Helmholtz Centre for Infection Research, ; Braunschweig, Germany

[12 ]GRID grid.452370.7, ISNI 0000 0004 0408 1805, TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, , a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, ; Hannover, Germany

[13 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Institute for Clinical and Experimental Transfusion Medicine, , University Hospital Tübingen, ; Tübingen, Germany

Author information

Matthias Becker http://orcid.org/0000-0002-9243-4257

Alex Dulovic http://orcid.org/0000-0003-0017-6738

Teresa R. Wagner http://orcid.org/0000-0002-1050-5948

Katja Schenke-Layland http://orcid.org/0000-0001-8066-5157

Gérard Krause http://orcid.org/0000-0003-3328-8808

Tamam Bakchoul http://orcid.org/0000-0002-6797-6812

Rolf Fendel http://orcid.org/0000-0003-4716-0311

Andrea Kreidenweiss http://orcid.org/0000-0002-5025-7221

Ulrich Rothbauer http://orcid.org/0000-0001-5923-8986

Michael Schindler http://orcid.org/0000-0001-8989-5813

Nicole Schneiderhan-Marra http://orcid.org/0000-0001-6785-181X

Article

Publisher ID: 23473

DOI: 10.1038/s41467-021-23473-6

PMC ID: 8149389

PubMed ID: 34035301

SO-VID: 882693f0-a35a-4283-a053-997957054735

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 : 8 March 2021

Date accepted : 28 April 2021

Funding

Funded by: FundRef https://doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft (German Research Foundation);

Award ID: DFG-KO 3884/5-1

Award Recipient : Michael Koeppen

Funded by: FundRef https://doi.org/10.13039/501100003542, Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (Ministry of Science, Research and Art Baden-Württemberg);

Funded by: FundRef https://doi.org/10.13039/501100009318, Helmholtz Association;

Award ID: SO-96

Award Recipient : Nicole Schneiderhan-Marra

Funded by: FundRef https://doi.org/10.13039/100010661, EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020);

Award ID: 101003480-CORESMA

Award Recipient : Nicole Schneiderhan-Marra

Funded by: FundRef https://doi.org/10.13039/501100011736, Ministerium für Wirtschaft, Arbeit und Wohnungsbau Baden-Württemberg (Ministry of Economics, Labor and Housing of Baden-Württemberg);

Award ID: FKZ-3-4332.62-NMI-67

Award ID: FKZ-3-4332.62-NMI-68

Award Recipient : Nicole Schneiderhan-Marra

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ScienceOpen disciplines: Uncategorized

Keywords: antibodies,vaccines,sars-cov-2

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ScienceOpen disciplines: Uncategorized

Keywords: antibodies, vaccines, sars-cov-2

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Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

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Novel Coronavirus Disease COVID-19

Most cited references 46

A Novel Coronavirus from Patients with Pneumonia in China, 2019

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

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Cited by 60

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