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1. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant.

Author

Graham C, Seow J, Huettner I, Khan H, Kouphou N, Acors S, Winstone H, Pickering S, Galao RP, Dupont L, Lista MJ, Jimenez-Guardeño JM, Laing AG, Wu Y, Joseph M, Muir L, van Gils MJ, Ng WM, Duyvesteyn HME, Zhao Y, Bowden TA, Shankar-Hari M, Rosa A, Cherepanov P, McCoy LE, Hayday AC, Neil SJD, Malim MH, and Doores KJ

Subjects
Angiotensin-Converting Enzyme 2 chemistry, Angiotensin-Converting Enzyme 2 metabolism, Antibodies, Monoclonal chemistry, Antibodies, Neutralizing immunology, Antibodies, Viral chemistry, COVID-19 diagnosis, Cross Reactions immunology, Epitopes chemistry, Epitopes genetics, Humans, Models, Molecular, Mutation, Neutralization Tests, Protein Binding immunology, Protein Conformation, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, Structure-Activity Relationship, Antibodies, Monoclonal immunology, Antibodies, Viral immunology, COVID-19 immunology, COVID-19 virology, Epitopes immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
Abstract

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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2. Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients.

Author

Abdul-Jawad S, Baù L, Alaguthurai T, Del Molino Del Barrio I, Laing AG, Hayday TS, Monin L, Muñoz-Ruiz M, McDonald L, Francos Quijorna I, McKenzie D, Davis R, Lorenc A, Chan JNE, Ryan S, Bugallo-Blanco E, Yorke R, Kamdar S, Fish M, Zlatareva I, Vantourout P, Jennings A, Gee S, Doores K, Bailey K, Hazell S, De Naurois J, Moss C, Russell B, Khan AA, Rowley M, Benjamin R, Enting D, Alrifai D, Wu Y, Zhou Y, Barber P, Ng T, Spicer J, Van Hemelrijck M, Kumar M, Vidler J, Lwin Y, Fields P, Karagiannis SN, Coolen ACC, Rigg A, Papa S, Hayday AC, Patten PEM, and Irshad S

Subjects
Adult, Aged, Aged, 80 and over, COVID-19 etiology, COVID-19 mortality, Female, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematologic Neoplasms virology, Humans, Immunophenotyping, Male, Middle Aged, Nasopharynx virology, Neoplasms mortality, Neoplasms therapy, Severe Acute Respiratory Syndrome etiology, Severe Acute Respiratory Syndrome mortality, Severe Acute Respiratory Syndrome virology, T-Lymphocytes virology, Virus Shedding, Young Adult, COVID-19 immunology, Neoplasms immunology, Neoplasms virology, Severe Acute Respiratory Syndrome immunology
Abstract

Given the immune system's importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19 + non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients' immunophenotypes resemble those of non-virus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Published
2021
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