Divergent Antibody Repertoires Found for Omicron versus Wuhan SARS-CoV-2 Strains Using Ig-MS

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Abstract

SARS-CoV-2 Omicron (B.1.1.529) and its subvariants are currently the most common variants of concern worldwide, featuring numerous mutations in the spike protein and elsewhere that collectively make Omicron variants more transmissible and more resistant to antibody-mediated neutralization provided by vaccination, previous infections, and monoclonal antibody therapies than their predecessors. We recently reported the creation and characterization of Ig-MS, a new mass spectrometry-based serology platform that can define the repertoire of antibodies against an antigen of interest at single proteoform resolution. Here, we applied Ig-MS to investigate the evolution of plasma antibody repertoires against the receptor-binding domain (RBD) of SARS-CoV-2 in response to the booster shot and natural viral infection. We also assessed the capacity for antibody repertoires generated in response to vaccination and/or infection with the Omicron variant to bind to both Wuhan- and Omicron-RBDs. Our results show that (1) the booster increases antibody titers against both Wuhan- and Omicron- RBDs and elicits an Omicron-specific response and (2) vaccination and infection act synergistically in generating anti-RBD antibody repertoires able to bind both Wuhan- and Omicron-RBDs with variant-specific antibodies.

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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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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C Walls, Young-Jun Park, M. Alejandra Tortorici … (2020)

Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Author and article information

Journal

Journal ID (nlm-ta): J Proteome Res

Journal ID (iso-abbrev): J Proteome Res

Journal ID (publisher-id): pr

Journal ID (coden): jprobs

Title: Journal of Proteome Research

Publisher: American Chemical Society

ISSN (Print): 1535-3893

ISSN (Electronic): 1535-3907

Publication date (Electronic): 07 November 2022

Electronic Location Identifier: acs.jproteome.2c00514

Affiliations

[† ]Proteomics Center of Excellence , Evanston, Illinois60208, United States

[‡ ]Department of Surgery, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois60611, United States

[§ ]Department of Molecular Biosciences, Chemistry, Northwestern University , Evanston, Illinois60208, United States

[⊥ ]Division of Infectious Diseases, Rush University Medical Center , Chicago, Illinois60612, United States

[¶ ]Department of Microbial Pathogens and Immunity, Rush University Medical Center , Chicago, Illinois60612, United States

[# ]Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine , Chicago, Illinois60611, United States

Author notes

[* ]Email: n-kelleher@ 123456northwestern.edu .

Author information

Benjamin J. Des Soye https://orcid.org/0000-0001-5480-4192

Michael A. R. Hollas https://orcid.org/0000-0002-0797-3134

Jared O. Kafader https://orcid.org/0000-0002-5359-264X

Beverly E. Sha https://orcid.org/0000-0002-9659-3554

Article

DOI: 10.1021/acs.jproteome.2c00514

PMC ID: 9668041

PubMed ID: 36343328

SO-VID: 38a7be65-b8d9-4662-adfd-bb3835e38438

License:

This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date received : 24 August 2022

Funding

Funded by: National Institute of General Medical Sciences, doi 10.13039/100000057;

Award ID: P41 GM108569

Funded by: Walder Foundation, doi NA;

Award ID: SCI16

Funded by: Walder Foundation, doi NA;

Award ID: 21-00650

Funded by: Walder Foundation, doi NA;

Award ID: 21-00147

Funded by: Research Corporation for Science Advancement, doi 10.13039/100001309;

Award ID: 27372

Custom metadata

document-id-old-9 pr2c00514

document-id-new-14 pr2c00514

ccc-price

ScienceOpen disciplines: Molecular biology

Keywords: antibodies,sars-cov-2,omicron variant,covid-19,ig-ms,serology

Data availability:

ScienceOpen disciplines: Molecular biology

Keywords: antibodies, sars-cov-2, omicron variant, covid-19, ig-ms, serology

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