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1.
J Immunol Methods ; 528: 113657, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38479453

RESUMO

Development of assays to reliably identify and characterize anti-drug antibodies (ADAs) depends on positive control anti-idiotype (anti-id) reagents, which are used to demonstrate that the standards recommended by regulatory authorities are met. This work employs a set of therapeutic antibodies under clinical development and their corresponding anti-ids to investigate how different positive control reagent properties impact ADA assay development. Positive controls exhibited different response profiles and apparent assay analytical sensitivity values depending on assay format. Neither anti-id affinity for drug, nor sensitivity in direct immunoassays related to sensitivity in ADA assays. Anti-ids were differentially able to detect damage to drug conjugates used in bridging assays and were differentially drug tolerant. These parameters also failed to relate to assay sensitivity, further complicating selection of anti-ids for use in ADA assay development based on functional characteristics. Given this variability among anti-ids, alternative controls that could be employed across multiple antibody drugs were investigated as a more uniform means to define ADA detection sensitivity across drug products and assay protocols, which could help better relate assay results to clinical risks of ADA responses. Overall, this study highlights the importance of positive control selection to reliable detection and clinical interpretation of the presence and magnitude of ADA responses.


Assuntos
Anticorpos Monoclonais , Antígenos , Imunoensaio/métodos
2.
Front Immunol ; 11: 1744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849622

RESUMO

Increasing evidence points to a role for antibody-mediated effector functions in preventing and controlling HIV infection. However, less is known about how these antibody effector functions evolve following infection. Moreover, how the humoral immune response is naturally tuned to recruit the antiviral activity of the innate immune system, and the extent to which these functions aid in the control of infection, are poorly understood. Using plasma samples from 10 hyper-acute HIV-infected South African women, identified in Fiebig stage I (the FRESH cohort), systems serology was performed to evaluate the functional and biophysical properties of gp120-, gp41-, and p24- specific antibody responses during the first year of infection. Significant changes were observed in both the functional and biophysical characteristics of the humoral immune response following acute HIV infection. Antibody Fc-functionality increased over the course of infection, with increases in antibody-mediated phagocytosis, NK activation, and complement deposition occurring in an antigen-specific manner. Changes in both antibody subclass and antibody Fc-glycosylation drove the evolution of antibody effector activity, highlighting natural modifications in the humoral immune response that may enable the directed recruitment of the innate immune system to target and control HIV. Moreover, enhanced antibody functionality, particularly gp120-specific polyfunctionality, was tied to improvements in clinical course of infection, supporting a role for functional antibodies in viral control.


Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , HIV/imunologia , Imunidade Humoral , Especificidade de Anticorpos , Biomarcadores/sangue , Proteínas do Sistema Complemento/imunologia , Feminino , Glicosilação , HIV/patogenicidade , Proteína do Núcleo p24 do HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Ativação Linfocitária , Monócitos/imunologia , Monócitos/virologia , Fagocitose , Prognóstico , Processamento de Proteína Pós-Traducional , Células THP-1 , Fatores de Tempo
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