Cellular immunity inducing vaccine

a cell-mediated immunity and vaccine technology, applied in the field of vaccines, can solve the problems of low antigen presentation efficiency, oil adjuvants, and inability to efficiently produce antitumor, and achieve the effects of high immune-inducing capacity, excellent ability to induce cell-mediated immunity, and high level

Inactive Publication Date: 2021-04-08
JAPANESE FOUND FOR CANCER RES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a peptide vaccine that can induce both cell-mediated immunity and humoral immunity. The peptide vaccine has a high immunogenicity and can be effective even when a peptide epitope has weak immunogenicity. The vaccine is effective for the treatment and prevention of diseases such as malaria, AIDS, and tumors that require cell-mediated immunity. The vaccine can be provided without using oil adjuvant and still induce a high level of immunity.

Problems solved by technology

However, since this method does not include the inherent process of antigen processing by dendritic cells or the like, the efficiency of antigen presentation may be low.
Moreover, it has recently been reported that oil adjuvants, which are indispensable for epitope peptide vaccines, cannot efficiently produce an antitumor effect since inflammation at the vaccination site causes localization of cytotoxic T cells (CTLs), which are responsible for attacking the tumor, in the vaccination site rather than the tumor site (Non-patent Document 5).
In these diseases, humoral immunity is not capable of responding to the diseases since specific antigens of the diseases are not expressed on the cell surface, where recognition by antibodies occur.
However, the types of antigens that are likely to undergo cross-presentation and details of the mechanism of this phenomenon are still unclear.

Method used

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  • Cellular immunity inducing vaccine
  • Cellular immunity inducing vaccine
  • Cellular immunity inducing vaccine

Examples

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examples

[0085]The present invention is described below more concretely based on Examples. However, the present invention is not limited to the Examples.

1. Design of Microgenes for Creating Artificial Proteins

[0086]From native antigen OVA (SEQ ID NO:24), OVA-I: ● (OVA MHC class I epitope, OVA258-265, SIINFEKL; SEQ ID NO: 67) and OVA-II: ▪ (OVA MHC class II epitope, OVA324-340, ISQAVHAAHAEINEAGR; SEQ ID NO: 2) were selected (FIG. 1a).

[0087]Microgenes #2101 and #6101, in which the MHC class I epitope OVA-I is encoded in the first sequence, and the MHC class II epitope OVA-II is encoded in the second sequence, were designed using CyberGene software, developed by Kiyotaka Shiba et al. (K. Shiba, Journal of Molecular Catalysis B: Enzymatic 28 (2004) 145-153) (FIG. 1b). The designing process is shown in 1) to 5) in FIG. 2. Since the two amino acids adjacent to the N-terminus of the MHC class I epitope (SIINFEKL) in native antigen OVA are known to influence degradation by aminopeptidase in the cell...

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Abstract

A novel vaccine that can induce sufficiently high cell-mediated immunity is disclosed. The vaccine of the present invention contains, as an effective component, a polypeptide comprising a tandem repeat structure in which an MHC class I epitope region derived from an antigen protein and a spacer sequence are linked to each other alternately and repeatedly at least three times, or a recombinant vector which comprises a polynucleotide encoding said polypeptide and is capable of expressing said polypeptide in vivo. The spacer sequence is, for example, a sequence generated as an amino acid sequence inevitably encoded by a single base sequence which is designed such that the MHC class I epitope region derived from the antigen protein, an MHC class II epitope region derived from the antigen protein, and at least one higher-order-structure-stabilizing region are encoded by different reading frames in said single base sequence.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. application Ser. No. 14 / 901,384 filed Feb. 29, 2016, which is the 371 National Phase of PCT International Application No. PCT / JP2014 / 067355, filed on Jun. 30, 2014, which claims priority under 35 U.S.C. 119(a) to Patent Application No. 2013-138688, filed in Japan on Jul. 2, 2013, all of which are hereby expressly incorporated by reference into the present application.TECHNICAL FIELD[0002]The present invention relates to a vaccine that can effectively induce cell-mediated immunity.BACKGROUND ART[0003]In recent years, tumor immunotherapy using an epitope peptide (minimal peptide sequence presented by an MHC class I or class II molecule) is attracting attention. Epitope peptide vaccines are administered in the form of a suspension of an epitope peptide in an oil emulsion such as Montanide. It is thought that, in such immunization, large amounts of the epitope peptide bind to empty MHC molecules of ant...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00C07K14/47C07K14/74
CPCA61K39/0011C07K19/00C07K14/70539A61K39/001153A61K39/00117A61K39/001124A61K39/001192A61K39/001106A61K39/00115A61K39/001156A61K39/001186A61K39/001191A61K39/001162A61K39/001188A61K39/001151A61K2039/62A61K2039/64Y02A50/30C07K14/4748A61P31/12A61P33/00A61P35/00
Inventor ITO, MASAKISHIBA, KIYOTAKA
Owner JAPANESE FOUND FOR CANCER RES
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