Use of phenol-soluble modulins for vaccine development

A technology for regulating protein and solubility, applied in the field of immunity

Inactive Publication Date: 2012-01-18
PROYECTO DE BIOMEDICINA CIMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] However, there is a need for further immunogenic compositions capable of (i) transporting antigen-derived T lymphocyte epitopes to APCs (or DCs) so that they can be loaded on MHC class I and / or MHC class II molecules, ( ii) Transmitting appropriate signals to DCs to induce their activation, since arrival of DCs from antigens in the absence of maturation signals will lead to tolerance without activation of helper T lymphocytes and cytotoxic T lymphocytes, ( iii) lead to effective immunogenicity regardless of prior immunity of the vector itself

Method used

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  • Use of phenol-soluble modulins for vaccine development
  • Use of phenol-soluble modulins for vaccine development
  • Use of phenol-soluble modulins for vaccine development

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0285] Example 1 Regulin peptides can bind to the cell surface of splenocytes. binding to regulatory proteins Subpopulations of white-derived peptides were analyzed.

[0286] Materials and methods

[0287] The peptides used in this experiment are listed in Table 3.

[0288] peptide

sequence

SEQ ID NO:

SIINFEKL

SIINFEKL

44

αMod

MADVIAKIVEIVKGLIDQFTQK

1

αMod-SIINFEKL

MADVIAKIVEIVKGLIDQFTQKSIINFEKL

45

SIINFEKL-αMod

SIINFEKLMADVIAKIVEIVKGLIDQFTQK

46

γMod

MAADIISTIGDLVKWIIDTVNKFKK

13

γMod-SIINFEKL

MAADIISTIGDLVKWIIDTVNKFKKSIINFEKL

47

SIINFEKL-γMod

SIINFEKLMAADIISTIGDLVKWIIDTVNKFKK

48

OVA (235-264)

ASGTMSMLVLLPDEVSGLEQLESIINFEKL

49

CFSE-γMod-SIINFEKL

CFSE-MAADIISTIGDLVKWIIDTVNKFKKSIINFEKL

47

CFSE-OVA(235-264)

CFSE-ASGTMSMLVLLPDEVSGLEQLESIINFEKL

49

1073

CVNGVCWTV

50

αMod-1073

...

Embodiment 2

[0295] Example 2 α- Regulin and γ-regulin activate dendritic cell maturation and antigen presentation Materials and methods

[0296] Generation of dendritic cells from bone marrow

[0297] Dendritic cells are grown from bone marrow cells. After lysing erythrocytes with ACK lysis reagent, the cells were washed and incubated with anti-CD4 (GK1; ATCC, Manassas, VA), CD8 (53.6.72; ATCC), Ly-6G / Gr1 (BD-Pharmingen; San Diego CA) and The CD45R / B220 (BD-Pharmingen) antibody mixture was incubated together to remove lymphocytes and granulocytes, followed by addition of rabbit-derived supplements. The remaining cells were grown in 12 Petri dishes using complete medium with 10 6 Cells / ml were supplemented with 20ng / ml mGM-CSF and 20ng / ml mIL-4 (both purchased from Peprotech; London, GB). Replace with fresh cytokine-containing medium every 2 days. On day 7, non-adherent dendritic cells were harvested and cultured in the presence or absence of 50 μM Modulin peptide or 1 μg / ml LPS ...

Embodiment 3

[0308] Example 3A - using a regulatory protein-derived peptide that binds to the cytotoxic SIINFEKL antigen with some Co-immunization with TLR ligands induces activation of cytotoxic responses to antigens. The cytotoxicity should The answer was long-lasting and protected mice against subcutaneous injection of EG7OVA1 tumor cells.

[0309] Materials and methods

[0310] Induction of cytotoxic T lymphocytes (CTL) in vivo and quantification of IFN-γ-producing cells after immunization (ELISPOT).

[0311] C57BL6 mice were immunized intravenously with 5nmol of the indicated peptide and 50μg of TLR3 ligand polymyocytes. In some cases, peptide immunization was performed in the presence of TLR2 (peptidoglycan), TLR4 (LPS or EDA protein) or TLR9 (CpG) ligands. Seven days after immunization, mice were injected intravenously with 5x10 6 A mixture of splenocytes, typically half of which were previously labeled with a 0.25 μM dose of C and the other half with 2.5 μM CFSE and SIIN...

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PUM

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Abstract

The invention relates to methods for enhancing the immunogenicity of an antigenic peptide by means of the covalent coupling thereof to a modulin-derived peptide (PSM, phenol-soluble modulin). In particular, bonding of the PSM[alpha], PSM[gamma] and PSM[delta] peptides to an antigen (originating from a pathogen or from a tumour-associated protein) enhances the capacity of the antigen to trigger an in vivo immune response. Thus, the PSM[alpha], PSM[gamma] and PSM[delta] peptides bound to said antigen can be used in vaccine development to prevent or to treat infectious diseases or cancer.

Description

technical field [0001] The present invention generally relates to the field of immunization, and in particular to a method for increasing the immunogenicity of an antigenic peptide by covalently binding the antigenic peptide to a modulatory protein-derived peptide (PSM, phenol-soluble modulatory protein). In particular, binding of PSMα, PSMγ, and PSMδ peptides to antigens (from pathogens or tumor-associated proteins) increases the ability of the antigens to activate an immune response in vivo. Therefore, PSMα, PSMγ and PSMδ peptides bound to these antigens can be used in the development of vaccines for the prevention or treatment of infectious diseases or cancer. technical background [0002] Pathogens and cancer remain the leading causes of death worldwide. Developing vaccines to prevent diseases for which there is no vaccine, such as AIDS or malaria, or to treat chronic diseases or cancer, as well as improving the efficacy and safety of existing vaccines, remains a priori...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/31A61K39/00
CPCA61K2039/6068A61K2039/55561C07K14/31C07K2319/00C07K14/47A61K39/385A61P31/04
Inventor 弗朗西斯科·博拉斯·奎斯塔伊纳斯·诺莉娅·卡萨雷斯·拉加尔马里亚德尔卡门·杜兰特斯·德尔加多胡安·何塞·拉萨尔特·萨加斯蒂韦尔萨克劳德·勒克莱尔赫苏斯·玛丽亚·普列托·巴尔图埃彻巴勃罗·萨罗韦·乌加里萨
Owner PROYECTO DE BIOMEDICINA CIMA
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