scholarly journals Recombinant rabbit single-chain antibodies bind to the catalytic and C-terminal domains of HIV-1 integrase protein and strongly inhibit HIV-1 replication

2012 ◽  
Vol 59 (5) ◽  
pp. 353-366 ◽  
Author(s):  
Frederico Aires da Silva ◽  
Min Li ◽  
Sylvie Rato ◽  
Sara Maia ◽  
Rui Malhó ◽  
...  
Keyword(s):  
Single Chain ◽  
Single Chain Antibodies ◽  
Hiv 1 ◽  
Integrase Protein ◽  
Terminal Domains

scholarly journals Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains

2011 ◽  
Vol 55 (5) ◽  
pp. 2369-2378 ◽  
Author(s):  
Jürgen Schanzer ◽  
Andreas Jekle ◽  
Junichi Nezu ◽  
Adriane Lochner ◽  
Rebecca Croasdale ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Bispecific Antibody ◽  
Bispecific Antibodies ◽  
Single Chain ◽  
Single Chain Antibodies ◽  
Physical Linkage ◽  
Antiviral Activities ◽  
Antibody Derivatives ◽  
Virus Strains ◽  
Hiv 1

ABSTRACTIn this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly4Ser)nsequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linkers, stable molecules could be obtained in amounts that were within the same range as or no less than 4-fold lower than those observed with monoclonal antibodies in transient expression assays. In contrast to monospecific CCR5 antibodies, bispecific antibody derivatives block two alternative docking sites of CCR5-tropic HIV strains on the CCR5 coreceptor. Consequently, these molecules showed 18- to 57-fold increased antiviral activities compared to the parent antibodies. Most importantly, one prototypic tetravalent CCR5 antibody had antiviral activity against virus strains resistant to the single parental antibodies. In summary, physical linkage of two CCR5 antibodies targeting different epitopes on the HIV coreceptor CCR5 resulted in tetravalent, bispecific antibodies with enhanced antiviral potency against wild-type and CCR5 antibody-resistant HIV-1 strains.

scholarly journals HIV-1-Specific Chimeric Antigen Receptors Based on Broadly Neutralizing Antibodies

2016 ◽  
Vol 90 (15) ◽  
pp. 6999-7006 ◽  
Author(s):  
Ayub Ali ◽  
Scott G. Kitchen ◽  
Irvin S. Y. Chen ◽  
Hwee L. Ng ◽  
Jerome A. Zack ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Neutralizing Antibodies ◽  
Binding Domain ◽  
Antigen Receptors ◽  
Single Chain ◽  
Broadly Neutralizing Antibodies ◽  
Chimeric Antigen Receptors ◽  
Single Chain Antibody ◽  
Single Chain Antibodies ◽  
Hiv 1

ABSTRACTAlthough the use of chimeric antigen receptors (CARs) based on single-chain antibodies for gene immunotherapy of cancers is increasing due to promising recent results, the earliest CAR therapeutic trials were done for HIV-1 infection in the late 1990s. This approach utilized a CAR based on human CD4 as a binding domain and was abandoned for a lack of efficacy. The growing number of HIV-1 broadly neutralizing antibodies (BNAbs) offers the opportunity to generate novel CARs that may be more active and revisit this modality for HIV-1 immunotherapy. We used sequences from seven well-defined BNAbs varying in binding sites and generated single-chain-antibody-based CARs. These CARs included 10E8, 3BNC117, PG9, PGT126, PGT128, VRC01, and X5. Each novel CAR exhibited conformationally relevant expression on the surface of transduced cells, mediated specific proliferation and killing in response to HIV-1-infected cells, and conferred potent antiviral activity (reduction of viral replication in log10units) to transduced CD8+T lymphocytes. The antiviral activity of these CARs was reproducible but varied according to the strain of virus. These findings indicated that BNAbs are excellent candidates for developing novel CARs to consider for the immunotherapeutic treatment of HIV-1.IMPORTANCEWhile chimeric antigen receptors (CARs) using single-chain antibodies as binding domains are growing in popularity for gene immunotherapy of cancers, the earliest human trials of CARs were done for HIV-1 infection. However, those trials failed, and the approach was abandoned for HIV-1. The only tested CAR against HIV-1 was based on the use of CD4 as the binding domain. The growing availability of HIV-1 broadly neutralizing antibodies (BNAbs) affords the opportunity to revisit gene immunotherapy for HIV-1 using novel CARs based on single-chain antibodies. Here we construct and test a panel of seven novel CARs based on diverse BNAb types and show that all these CARs are functional against HIV-1.

Human Single-Chain Antibodies Inhibit Replication of Human Immunodeficiency Virus Type 1 (HIV-1)

2005 ◽  
Vol 21 (10) ◽  
pp. 876-881 ◽  
Author(s):  
Fangbing Liu ◽  
Mukesh Kumar ◽  
Qiangzhong Ma ◽  
Mark Duval ◽  
David Kuhrt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Single Chain ◽  
Single Chain Antibodies ◽  
Immunodeficiency Virus ◽  
Hiv 1

Targeting of HIV-1 Tat traffic and function by transduction-competent single chain antibodies

Vaccine ◽  
2006 ◽  
Vol 24 (16) ◽  
pp. 3127-3136 ◽  
Author(s):  
D THEISEN ◽  
C PONGRATZ ◽  
K WIEGMANN ◽  
F RIVERO ◽  
O KRUT ◽  
...  
Keyword(s):  
Single Chain ◽  
Single Chain Antibodies ◽  
And Function ◽  
Hiv 1

scholarly journals Construction of single-chain antibodies that bind an overlapping epitope of HIV-1 Nef

FEBS Letters ◽  
1998 ◽  
Vol 441 (2) ◽  
pp. 307-312 ◽  
Author(s):  
Alex H Chang ◽  
James A Hoxie ◽  
Sharon Cassol ◽  
Michael O'Shaughnessy ◽  
Frank Jirik
Keyword(s):  
Single Chain ◽  
Single Chain Antibodies ◽  
Hiv 1

scholarly journals Identification of single chain antibodies to breast cancer stem cells using phage display

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Deniz Gur ◽  
Suling Liu ◽  
Anurag Shukla ◽  
Stephanie C Pero ◽  
Max S Wicha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Phage Display ◽  
Breast Cancer Stem Cells ◽  
Single Chain ◽  
Single Chain Antibodies

Optimization of the expression of single-chain antibodies using different Escherichia coli systems

2007 ◽  
Vol 131 (2) ◽  
pp. S251-S252
Author(s):  
Symon Riedstra ◽  
Gonçalo Leite ◽  
Carolina Ferreira ◽  
Francisco Brás Gomes ◽  
Paulo M.P. Costa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Single Chain ◽  
Single Chain Antibodies

scholarly journals Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly

2005 ◽  
Vol 79 (23) ◽  
pp. 14498-14506 ◽  
Author(s):  
Ayna Alfadhli ◽  
Tenzin Choesang Dhenub ◽  
Amelia Still ◽  
Eric Barklis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protein Assembly ◽  
Particle Assembly ◽  
Gag Protein ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Terminal Domains

ABSTRACT The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.

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