Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humansa phase I evaluation
作者:
Gabriela Stiegler,
Christine Armbruster,
Brigitta Vcelar,
Heribert Stoiber,
Renate Kunert,
Nelson Michael,
Linda Jagodzinski,
Christoph Ammann,
Walter Jäger,
Jeffrey Jacobson,
Norbert Vetter,
Hermann Katinger,
期刊:
AIDS
(OVID Available online 2002)
卷期:
Volume 16,
issue 15
页码: 2019-2025
ISSN:0269-9370
年代: 2002
出版商: OVID
关键词: HIV-1;human monoclonal antibodies;antiviral effects;HIV therapy
数据来源: OVID
摘要:
Background:The human monoclonal antibodies (MAbs) 2F5 and 2G12 were identified to be two of the most potent neutralizing antibodies against HIV-1. In a first human study they have been shown to be safe after repeated intravenous infusions to asymptomatic HIV-1-infected individuals. However, the antiviral effects of antibody treatment have not been fully analyzed in this first clinical trial.Methods:The aim of the present study was to gain a preliminary insight into the antiviral effects of 2F5 and 2G12 in humans. For this purpose, plasma samples obtained from the previous phase I study were studied for RNA copy numbers by reverse transcriptase-polymerase chain reaction. As a measure for activation of complement levels of the major complement factor C3 were measured by enzyme-linked immunosorbent assay. Flow cytometry was used to study T-lymphocyte counts and the amount of infected peripheral blood mononuclear cells (PBMC) was determined by co-culture with uninfected donor PBMC. Virus escape from antibody neutralization was determinedin vitroin a PBMC neutralization assay.Results:Transient reduction in viral loads was observed in five of seven patients. Vigorous complement activation was observed directly after HIV-specific antibody infusions. The number of infective peripheral blood mononuclear cells was reduced in some patients whereas CD4+ T-lymphocyte counts and CD4+/CD8+ ratios were transiently increased in all patients. Virus escape occurred only against 2G12.Conclusions:Analysis of disease progression markers indicate that antibody therapy may have antiviral effects. These findings suggest that neutralizing antibodies should be further evaluated as an alternative therapeutic approach in HIV-1 disease.
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