Chimeric peptide immunogens

a technology of chimeric peptides and immunogens, applied in the field of chimeric peptides, can solve the problem of not being regarded promiscuous enough to be applicable to a large number of patients

Inactive Publication Date: 2007-08-09
GRIMES STEPHEN +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the promiscuous helper T-cell (Th)-epitope candidate T1 (TT sequence 947-967 aa, SEQ ID NO: 4) was not regarded promiscuous enough to be applicable for a large number of animal species.

Method used

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  • Chimeric peptide immunogens
  • Chimeric peptide immunogens
  • Chimeric peptide immunogens

Examples

Experimental program
Comparison scheme
Effect test

example i

[0025] The peptide sequences combine a select promiscuous T-helper-epitope through an inserted short spacer peptide (e.g., 4-8 amino acids) with at least one target hormone peptide. Suitable spacers of this invention include but are not limited to the peptides comprising the following amino acid sequence, GPSL (see SEQ ID NO: 5); SSGPSL (SEQ ID NO: 6); and SSGPSLKL (SEQ ID NO: 7), which are inserted in the peptide chimera to isolate the three dimensional folding of the immunogenic peptide from that of the hormone peptide.

[0026] Promiscuous Th-epitope moieties from measles virus protein F (MSF) (sequence 288-302 aa, SEQ ID NO: 8), tetanus toxoid (TT) (sequence 947-967 aa, SEQ ID NO: 4, or sequence 830-844 aa, SEQ ID NO: 2) and malaria Plasmodium falciparum CSP protein (sequence 378-398 aa, SEQ ID NO: 3) are used in these constructs. The hormone immunomimic epitopes were attached to the N-terminal or the C-terminus of the spacer as shown below. All mammalian GnRH peptides including t...

example ii

[0027] Immunogenicity tests were performed with five chimeric peptide immunogens against GnRH. Each chimeric peptide contained one region encoding an epitope to be recognized by helper T-cell and a second region encoding an immunomimic of GnRH, to serve as the target for the antibody response. The chimeric peptide immunogens were formulated to deliver 100, 250 or 500 μg doses of peptide with 3 μg norMDP, in a water in oil emulsion. Control immunogens were prepared to deliver 500 μg of mammalian GnRH (1-10) Ser1 peptide (which is normally linked to an immunogenic carrier to impart immunogenicity), with and without norMDP (3 μg), in the same emulsions. The immunogens were given intramuscularly to rabbits in three injections, on days 0, 14 and 42. An ELISA procedure was used to measure the resultant anti-GnRH antibody responses in sera collected at 14-day intervals over the course of the immunization. Injection site reactions were assessed by visual and microscopic evaluations on day 8...

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Abstract

Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.

Description

[0001] This application claims priority from the provisional application No. 60 / 202,328, filed May 5, 2000 in the United States Patent and Trademark Office.FIELD OF THE INVENTION [0002] The invention is related to chimeric peptides having immunogenic efficacy, comprising a hormone epitope and promiscuous helper T-cell epitope for the production of high titers of anti-hormone antibodies. BACKGROUND OF THE INVENTION [0003] The success of an antigenic composition is linked to its immunogenicity, that is, the ability to produce a sufficiently high titer of antibodies to react or bind with the target antigen or so as to neutralize its effects. The immunogenicity depends on the effectiveness by which the antigen causes the body's immune system to mount a response which can be generally assessed on the basis of the antibody titer in the blood of the immunized animal or mammal including the human. [0004] Antigenic formulations can be prepared for antigens of low immunogenicity with construc...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K39/12A61K39/00A61K39/395A61P5/00A61P5/02A61P13/08A61P35/00A61P37/02A61P43/00C07K7/23C07K14/575C07K19/00
CPCA61K39/00A61K39/0006A61K2039/6031C07K2319/00A61K2039/6068C07K7/23A61K2039/6037A61P13/08A61P35/00A61P37/02A61P43/00A61P5/00A61P5/02Y02A50/30
InventorGRIMES, STEPHENMICHAELI, DOVSTEVENS, VERNON C.
OwnerGRIMES STEPHEN