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.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Ji C,Brandt M,Dioszegi M,Jekle A,Schwoerer S,Challand S,Zhang J,Chen Y,Zautke L,Achhammer G,Baehner M,Kroetz S,Heilek-Snyder G,Schumacher R,Cammack N,Sankuratri Sdoi
10.1016/j.antiviral.2006.11.003subject
Has Abstractpub_date
2007-05-01 00:00:00pages
125-37issue
2eissn
0166-3542issn
1872-9096pii
S0166-3542(06)00342-1journal_volume
74pub_type
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