Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: a phase I evaluation.
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 an alternative therapeutic approach in HIV-1 disease.
Stiegler
Gabriela
G
Institute of Applied Microbiology, University of Agricultural Sciences, Muthgasse, Vienna, Austria. G.Stiegler@iam.boku.ac.at
Armbruster
Christine
C
Vcelar
Brigitta
B
Stoiber
Heribert
H
Kunert
Renate
R
Michael
Nelson L
NL
Jagodzinski
Linda L
LL
Ammann
Christoph
C
Jäger
Walter
W
Jacobson
Jeffrey
J
Vetter
Norbert
N
Katinger
Hermann
H
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003167:Complement Activation; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007116:Immunization, Passive; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D012367:RNA, Viral