Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities.
Antiviral Res
; 74(2): 125-37, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17166600
ABSTRACT
To identify monoclonal antibodies (mAbs) with high potency and novel recognition sites, more than 25,000 of mouse hybridomas were screened and 4 novel anti-human CCR5 mAbs ROAb12, ROAb13, ROAb14, and ROAb18 showing potent activity in cell-cell fusion (CCF) assay were identified. These mAbs demonstrated potent antiviral activities in both single-cycle HIV infection (IC(50) range 0.16-4.3 microg/ml) and PBMC viral replication (IC(50) range 0.02-0.04 microg/ml) assays. These potent antiviral effects were donor-independent. All 4 mAbs were also highly potent in the PhenoSense assay against 29 HIV isolates covering clade A through G. In all antiviral assays, these mAbs showed potency superior to the previously reported mAb 2D7 in side-by-side comparison studies. All 4 mAbs were also fully active against viruses resistant to HIV fusion inhibitor enfuvirtide and CCR5 antagonist maraviroc. Although ROAb12, ROAb14, and ROAb18 inhibited RANTES, MIP1alpha and MIP1beta binding and cell activation, the other novel mAb ROAb13 was inactive in inhibiting cell activation by these three ligands. Furthermore, highly synergistic antiviral effects were found between mAb ROAb13 and 2D7 or ROAb12. In addition, none of these mAbs showed agonist activity or caused internalization of the CCR5 receptor.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
HIV
/
Fármacos Anti-HIV
/
Receptores CCR5
/
Anticorpos Monoclonais
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos