Synthetic peptides that bind to the hepatitis B virus core and E antigens

a technology of hepatitis b virus and e antigen, applied in the field of synthetic peptides that bind to the hepatitis b virus core and e antigen, can solve the problems of varying the degree of acute liver injury, and achieve the effect of modulating the host immune respons

Inactive Publication Date: 2006-01-26
SALLBERG MATTI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0007] Methods to characterize binding partners are also embodiments. The term “characterization assay” is used to refer to an experiment or evaluation of the ability of a candidate binding partner and / or binding partner to interact with HBcAg and / or HBeAg, inhibit HBV infection, or modulate a host immune response. Some characterization assays, for example, evaluate the ability of a binding partner to bind to a multimeric agent having HBcAg and / or HBeAg disposed thereon or vice versa. Other characterization assays access the ability of a binding partner to fix complement and / or bind to a high titer antibody. Additional characterization assays determine whether a binding partner can effect viral infection in cultured cell lines or infected animals. Still further, some embodiments evaluate the ability of a binding partner to modulate a host immune system response, as measured by cytokine production and / or T cell proliferation.

Problems solved by technology

Primary infection may be asymptomatic (e.g., in chronically infected individuals) or may result in varying degrees of acute liver injury.

Method used

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  • Synthetic peptides that bind to the hepatitis B virus core and E antigens

Examples

Experimental program
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example 1

[0039] The mAbs that were used to create the binding partners specific for HBcAg and / or HBeAg were made by conventional techniques, as described above, using recombinant peptides. Full length recombinant HBcAg (rHBcAg) encompassing residues 1-183 was produced in Escherichia coli, as previously described. (Schodel et al., J Biol Chem, 268:1332-7 (1993), herein expressly incorporated by reference in its entirety). A truncated recombinant form of HBeAg containing nine residues of pre-core and the 150 first residues of HBcAg was also made. Further, a non-structural 3 protein (NS3) of the hepatitis C virus (HCV) was also made to serve as a control. (Jin and Peterson, Arch. Biochem. Biophys., 323:47-53 (1995), herein expressly incorporated by reference in its entirety). Another control peptide, an analogue of HBcAg (ΔHBcAg), wherein region 76-85 was replaced by an irrelevant sequence, was also made.

[0040] Balb / c and CBA mice (purchased from BK Universal, Sollentuna, Sweden) were immunize...

example 2

[0042] To determine the reactivity and specificity of a mAb, recombinant proteins or fragments thereof (e.g., HBcAg, HBeAg, ΔHBcAg, denatured HBcAg, or NS3 proteins) were passively adsorbed at 10 μg / ml to 96 well microtiter plates in 50 mM sodium carbonate buffer, pH 9.6, overnight at 4° C. Serial dilutions of mAbs were made in phosphate buffered saline (PBS) containing 2% goat serum (Sigma Chemicals, St Louis, Mo.), and 0.05% Tween 20 (PBS-GT). The various dilutions were then incubated on the plates for 60 minutes. Bound mAbs were detected either by rabbit anti-mouse IgG (Sigma), or rabbit anti-mouse IgG1, IgG2a, IgG2b or IgG3 (Sigma) followed by a peroxidase labeled goat anti-rabbit IgG (Sigma). The plates were developed by incubation with dinitro-phenylene-diamine (Sigma) and the absorbance at 490 nm was determined. Additionally, the reactivity in Abbott anti-HBc and HBe IMX assays was determined according to the manufacturer's instructions. The results of these studies are provi...

example 3

[0044] To determine the protein sequence of an antibody binding domain, total cellular mRNA was extracted using magnetic beads coated with oligo-dT25 (Dynal A. S, Oslo, Norway). The variable domains of the heavy (VH) and light (VL) chains of mAbs were amplified from cDNA by the Polymerase Chain Reaction (PCR) using the recombinant phage antibody system (Pharmacia Biotech, Uppsala, Sweden). The amplified cDNA fragments were directly ligated to the TA cloning vector pCR 2.1 (Invitrogen, San Diego, USA) as described. (Zhang et al., Clin. Diagn. Lab. Immunol., 7:58-63 (2000), herein expressly incorporated by reference in its entirety). The DNA sequences were determined by an automated sequencer (ALF express, Pharmacia, Uppsala, Sweden) as described. (Zhang et al., Clin. Diagn. Lab. Immunol., 7:58-63 (2000), herein expressly incorporated by reference in its entirety). From the cDNA sequence, a corresponding protein sequence was deduced. The protein sequences deduced from VH cDNA clones o...

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Abstract

The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides, which bind to the Hepatitis B virus (HBV) core and e antigens, can be used to inhibit HBV infection. Embodiments concern “binding partners”, which include peptides, peptidomimetics, and chemicals that resemble these molecules that interact with HBV core and e antigens, biological complexes having HBV core and e antigens joined to said binding partners, methods of identifying such binding partners, pharmaceuticals having binding partners, and methods of treatments and prevention of HBV infection.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 10 / 369,060, filed Feb. 14, 2003, which is a continuation of U.S. application Ser. No. 09 / 839,447, filed Apr. 20, 2001, now abandon, which is a continuation-in-part of U.S. Pat. No. 6,417,324, issued Jul. 9, 2002. This application claims the benefit of priority to U.S. application Ser. Nos. 10 / 369,060 and 09 / 839,447 and U.S. Pat. No. 6,417,324, all of which are hereby expressly incorporated by reference in their entireties.FIELD OF THE INVENTION [0002] The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides that bind to the hepatitis B virus (HBV) core and e antigens can be used to inhibit HBV infection. BACKGROUND OF THE INVENTION [0003] Of the many viral causes of human hepatitis, few are of greater global importance than hepatitis B virus (HBV). Approximately 300 million people worldwide are...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C07K9/00A61K38/14C07K7/06C07K7/08C07K14/02C07K16/08
CPCA61K38/00A61K2039/505C07K7/06C07K7/08C12N2730/10122C07K16/082C07K2317/50C07K2317/56C07K14/005Y02A50/30
Inventor SALLBERG, MATTI
Owner SALLBERG MATTI
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