Recombinant human Fab antibody fragments to HIV-1 Rev and Tat regulatory proteins: Direct selection from a combinatorial phage display library

Pilkington, Glenn; Duan, Lingxun; Zhu, Minghua; Keil, Walter; Pomerantz, Roger J.

doi:10.1016/0161-5890(95)00153-0

Cited by 19 publications

(12 citation statements)

References 30 publications

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“…[6][7][8][9] Via inhibition of different viral targets, the HIVappears to function as a series of genes and genetic 1 life-cycle can now be specifically inhibited at pre-or elements within HIV-1-infected patients. As such, the post-integration stages in cell culture.…”

Section: Introductionmentioning

confidence: 99%

Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based strategy

et al. 1997

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Exporting unspliced human immunodeficiency virus type 1 function, thereby inhibiting viral replication. In the present (HIV-1) RNA from the nucleus to the cytoplasm, through studies, different HIV-1 RRE region-specific hammerhead an interaction between the viral regulatory Rev protein and ribozymes were constructed and their anti-HIV-1 repliRev response element (RRE) RNA, is a critical step in the cation effects were assayed in diverse RNA polymerase HIV-1 life-cycle. Disruption of either Rev or the RRE will (pol) II and III promoters and vector systems in cell culture. completely inhibit HIV-1 replication. As such, a strategy for Utilizing this combination of an SFv and a ribozyme as a somatic gene therapy to treat HIV-1 infection by intracelludual strategy to block HIV-1 replication, both at the protein lar expression of an anti-HIV-1 Rev single chain variable and RNA level, data from these studies demonstrated that fragment (SFv) and a ribozyme which specifically targets potent inhibition of HIV-1 replication can be achieved via the RRE was developed. The anti-Rev D8SFv, which this approach. Combination gene therapies hold promise, specifically targets the Rev activation domain, may be a analogous to combination chemotherapeutic regimens, for key component of combination intracellular immunization, the in vivo treatment of HIV-1 infections. as it has been previously shown to potently inhibit Rev

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Section: Introductionmentioning

confidence: 99%

Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based strategy

et al. 1997

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“…We sought to compare the frequency of mutation in F4 ϩ heavy chain V H genes to that in protective antibodies encoded by the same V H genes derived from nonautoimmune individuals (Table VI) (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). No significant difference between the two groups was found; F4 ϩ V H genes contained 194 mutations in 10 sequences, while 437 mutations were present in 24 sequences from nonautoimmune individuals (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Lupus-specific antibodies reveal an altered pattern of somatic mutation.

Manheimer-Lory

Zandman‐Goddard²,

Davidson³

et al. 1997

J. Clin. Invest.

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The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA. Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4ϩ IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation. This molecular analysis of F4 ϩ B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent V H gene restriction. Furthermore, V H gene segments encoding these antibodies are also used in protective immune responses.An examination of the process of somatic mutation in F4 ϩ antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions. However, there was a decrease in targeting of mutations to putative mutational hot spots. This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection. (

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“…Suitable therapeutic agents such as human monoclonally specific antibodies able to bind strongly to the extracellular Tat can conceivably be capable of inhibiting the deleterious functions of Tat. Only two previous reports described human MAbs (HMAbs) against Tat (19,24). Here we describe the generation of five new HMAbs directed against the two key epitopes of Tat, two complete IgGs and three single-chain fragmentvariable (scFv) antibodies, and we assess their abilities to block Tat-induced transactivation and viral replication.…”

mentioning

confidence: 99%

Generation and Characterization of Neutralizing Human Monoclonal Antibodies against Human Immunodeficiency Virus Type 1 Tat Antigen

Moreau

Hoebeke

Zagury

et al. 2004

J Virol

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The human immunodeficiency virus Tat regulatory protein is essential for virus replication and pathogenesis. From human peripheral blood mononuclear cells of three Tat toxoid-immunized volunteers, we isolated five Tat-specific human monoclonal antibodies (HMAbs): two full-length immunoglobulin G (IgG) antibodies and three single-chain fragment-variable (scFv) antibodies. The two IgGs were mapped to distinct epitopes within the basic region of Tat, and the three scFvs were mapped to the N-terminal domain of Tat. The three scFvs were highly reactive with recombinant Tat in Western blotting or immunoprecipitation, but results were in contrast to those for the two IgGs, which are sensitive to a particular folding of the protein. In transactivation assays, scFvs were able to inhibit both active recombinant Tat and native Tat secreted by a transfected CEM cell line while IgGs neutralized only native Tat. These HMAbs were able to reduce viral p24 production in human immunodeficiency virus type 1 strain IIIB chronically infected cell lines in a dose-dependent manner.

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Recombinant human Fab antibody fragments to HIV-1 Rev and Tat regulatory proteins: Direct selection from a combinatorial phage display library

Cited by 19 publications

References 30 publications

Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based strategy

Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based strategy

Lupus-specific antibodies reveal an altered pattern of somatic mutation.

Generation and Characterization of Neutralizing Human Monoclonal Antibodies against Human Immunodeficiency Virus Type 1 Tat Antigen

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