Bamlanivimab treatment leads to rapid selection of immune escape variant carrying E484K mutation in a B.1.1.7 infected and immunosuppressed patient

ABSTRACT In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the “a” determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P = 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of “a” determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

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Erratum to: Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce “danger signals”

Breast Cancer Research and Treatment ◽

10.1007/s10549-006-9163-6 ◽

2006 ◽

Vol 96 (3) ◽

pp. 243-243 ◽

Cited By ~ 1

Author(s):

Masoud H. Manjili ◽

Hilal Arnouk ◽

Keith L. Knutson ◽

Maciej Kmieciak ◽

Mary L. Disis ◽

...

Keyword(s):

Immune Escape ◽

Mammary Tumors ◽

Proteomic Profile ◽

Escape Variant ◽

Danger Signals

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First description of two immune escape indian B.1.1.420 and B.1.617.1 SARS-CoV2 variants in France

10.1101/2021.05.12.443357 ◽

2021 ◽

Author(s):

Vincent Garcia ◽

Veronique Vig ◽

Laurent Peillard ◽

Alaa Ramdani ◽

Sofiane Mohamed ◽

...

Keyword(s):

Immune Escape ◽

Close Monitoring ◽

Infected People ◽

Gene Coding ◽

Fast Spreading ◽

History Of ◽

Travel Abroad ◽

First Time ◽

Induced Immunity ◽

Selection Of

Following the outbreak of the SARS-CoV2 virus worldwide in 2019, the rapid widespread overtime of variants suggests today an undergoing positive selection of variants which could potentially provide advantageous genetic property of the virus. Numerous variants have already been described across different countries including N501Y, E484K or L452R mutations on gene coding to spike protein. Most recently, 2 new Indian variants with N440K and E484Q and L452R mutations associated with impaired antibody response and immune reactions were identified in India. The potential consequences of emerging variants are increased transmissibility, increased pathogenicity and the ability to escape natural or vaccine-induced immunity. We described for the first time in France both variants: the N440K immune escape variant within a new strain detected in France in a couple of patients who did not have any history of travel abroad and the new E484Q and L452R Indian variant from a patient travelling from Indian to Marseille to embark on a ship as a crew member. Such study of the circulating viral strains and their variants within the increasing number of infected people worldwide will provide further insights into the viral dissemination. Hence, real time close monitoring variant could help the scientific community to prevent fast-spreading and raise alarms towards potentially harmful variants.

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Selection of an escape variant of Borrelia burgdorferi by use of bactericidal monoclonal antibodies to OspB.

Infection and Immunity ◽

10.1128/iai.60.8.3098-3104.1992 ◽

1992 ◽

Vol 60 (8) ◽

pp. 3098-3104 ◽

Cited By ~ 54

Author(s):

J L Coleman ◽

R C Rogers ◽

J L Benach

Keyword(s):

Monoclonal Antibodies ◽

Borrelia Burgdorferi ◽

Escape Variant ◽

Selection Of

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Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants

Nature Communications ◽

10.1038/s41467-021-26602-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sebastian Weigang ◽

Jonas Fuchs ◽

Gert Zimmer ◽

Daniel Schnepf ◽

Lisa Kern ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Immune Escape ◽

Kidney Transplant Recipient ◽

Immunosuppressive Treatment ◽

Escape Variant ◽

Persistent Infections ◽

Infection Dynamics ◽

Next Generation Sequencing Ngs ◽

Host Evolution

AbstractThe origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient’s escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.

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Characterization of Primary and Immune Escape Variant of HER-2/neu Overexpressing Mouse Mammary Carcinoma

Journal of Immunotherapy ◽

10.1097/01.cji.0000191056.58264.74 ◽

2005 ◽

Vol 28 (6) ◽

pp. 646

Author(s):

Masoud Manjili ◽

Maciej Kmieciak

Keyword(s):

Mammary Carcinoma ◽

Immune Escape ◽

Mouse Mammary Carcinoma ◽

Escape Variant ◽

Her 2

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Stabilizing selection of seasonal influenza receptor binding in populations with partial immunity

10.1101/2020.06.27.175190 ◽

2020 ◽

Author(s):

James A. Hay ◽

Alvin Junus ◽

Steven Riley ◽

Hsiang-Yu Yuan

Keyword(s):

Phylogenetic Analysis ◽

Receptor Binding ◽

Seasonal Influenza ◽

Immune Escape ◽

Stabilizing Selection ◽

Human Influenza ◽

Net Charge ◽

Binding Avidity ◽

Selection Of ◽

Partial Immunity

AbstractMutations that alter cellular receptor binding of influenza hemagglutinin (HA) have profound effects on immune escape. Despite its high mutation rate, it is not fully understood why human influenza HA displays limited antigenic diversity across circulating viruses. We applied phylogenetic analysis and phylodynamic modeling to understand the evolutionary and epidemiological effects of binding avidity adaptation in humans using net charge as a marker for receptor binding avidity. Using 686 human influenza A/H3N2 HA sequences, we found that HA net charge followed an age-specific pattern. Phylogenetic analysis suggested that many binding variants have reduced fitness. Next, we developed an individual-based disease dynamic model embedded with within-host receptor binding adaptation and immune escape in a population with varied partial immunity. The model showed that mean binding avidity was unable to adapt to values that maximized transmissibility due to competing selective forces between within- and between-host levels. Overall, we demonstrated stabilizing selection of virus binding in a population with increasing partial immunity. These findings have potential implications in understanding the evolutionary mechanisms that determine the intensity of seasonal influenza epidemics.

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