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Stiegler, G; Armbruster, C; Vcelar, B; Stoiber, H; Kunert, R; Michael, NL; Jagodzinski, LL; Ammann, C; J├Ąger, W; Jacobson, J; Vetter, N; Katinger, H; .
(2002): Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: a phase I evaluation.
AIDS. 2002; 16(15):2019-2025

Abstract:
Background: The human monoclonal antibodies (MAbs) 2F5 and 2612 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 'symptomatic 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 2612 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 determined in vitro in 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. (C) 2002 Lippincott Williams Wilkins.
Authors BOKU Wien:
Katinger Hermann
Kunert Renate
Find related publications in this database (using NML MeSH Indexing)
Adult;Antibodies, Monoclonal/administration & dosage;Antibodies, Monoclonal/immunology;Antibodies, Monoclonal/therapeutic use*;CD4 Lymphocyte Count;Complement Activation;Female;HIV Antibodies/administration & dosage;HIV Antibodies/immunology;HIV Antibodies/therapeutic use*;HIV Infections/therapy*;HIV Infections/virology;HIV-1/immunology;HIV-1/physiology;Humans;Immunization, Passive*;Leukocytes, Mononuclear/virology;Male;Middle Aged;Neutralization Tests;RNA, Viral/blood;Viral Load*;

Find related publications in this database (Keywords)
HIV-1
human monoclonal antibodies
antiviral effects
HIV therapy


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