Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: A phase I evaluation

Gabriela Stiegler*, Christine Armbruster, Brigitta Vcelar, Heribert Stoiber, Renate Kunert, Nelson L. Michael, Linda L. Jagodzinski, Christoph Ammann, Walter Jäger, Jeffrey Jacobson, Norbert Vetter, Hermann Katinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

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 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 ah alternative therapeutic approach in HIV-1 disease.

Original languageEnglish
Pages (from-to)2019-2025
Number of pages7
JournalAIDS
Volume16
Issue number15
DOIs
StatePublished - 18 Oct 2002
Externally publishedYes

Keywords

  • Antiviral effects
  • HIV therapy
  • HIV-1
  • Human monoclonal antibodies

Fingerprint

Dive into the research topics of 'Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: A phase I evaluation'. Together they form a unique fingerprint.

Cite this