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VACCINE AGAINST PATHOGENIC GRAM-NEGATIVE BACTERIA

Foreign code F190009792
File No. S2017-0291-C0
Posted date May 8, 2019
Country WIPO
International application number 2018JP003991
International publication number WO 2018147265
Date of international filing Feb 6, 2018
Date of international publication Aug 16, 2018
Priority data
  • P2017-020501 (Feb 7, 2017) JP
Title VACCINE AGAINST PATHOGENIC GRAM-NEGATIVE BACTERIA
Abstract The present invention provides a vaccine against pathogenic gram-negative bacteria, the vaccine comprising a V antigen of a type III secretion system, a homolog protein thereof, a part thereof, or a gene encoding the V antigen, and a CpG oligodeoxynucleotide (CpG ODN) adjuvant.
Outline of related art and contending technology BACKGROUND ART
In accordance with the aging and highly advanced medical, multi-drug resistant bacteria by many lethal infection has been reported. In particular, opportunistic infections and ventilator-associated pneumonia intensive target high frequency of disease-bacteria-resistant Pseudomonas aeruginosa highly rapidly advanced and multi-agent, an antimicrobial agent that does not rely on, to enhance the immunity to the vaccine development is in strong demand.
Pseudomonas aeruginosa many pathogenic gram negative bacteria, eukaryotic cells and in direct contact with the target, type III secretion system (TTSS) special used, directly, in the cytoplasm of the target protein toxin is transferred to (Fig. 1). Is against the pathogenic, not antibody to a toxin, toxin secretion inhibition or, the enzymatic action of toxin or transition needs to be suppressed. Pseudomonas aeruginosa is one toxin 4 through the TTSS (ExoS, T, U, Y) is injected into the target cell results in the inhibition or cell death to phagocytize the toxicological agents (Fig. 2) (Non-Patent Document 1). Toxin is injected into the target cell of the quality, type III secretion system structure of the tip of the target cell is formed on the pores is required, these are one of the 3 protein (PcrV, PopB, PopD) (Fig. 3) is configured. Particularly PcrV the protein, and antigen homolog of Yersinia pestis LcrV and V, the present inventor et al. has the effect of vaccines against Pseudomonas aeruginosa infection was found (Non-Patent Document 2). After, the secretion of the type III secretion system PcrV of the pentamer cap portion at a leading end of the protrusion (Fig. 3) constituting the structure, specific antibodies PcrV toxin (Non-Patent Document 3-5) of the pores have been found to inhibit the passage. The present inventors have found this to result in an animal model antibody therapy, bacteriological human, on the basis of epidemiologic such as serum, human vaccines for Pseudomonas aeruginosa is applicable to clinical development has been performed (non-patent document 6-7).
Scope of claims (In Japanese)請求の範囲 [請求項1]
少なくとも1種のIII型分泌システムのV抗原又はその相同体タンパク質又はその一部もしくはそれをコードする遺伝子とアジュバントとして少なくとも1種のCpGオリゴデオキシヌクレオチド(CpG ODN)を含む病原性グラム陰性菌に対するワクチン。

[請求項2]
III型分泌システムのV抗原又はその相同体タンパク質が、PcrV、LcrV、LssV、AcrV、VcrV、EspA、SipD、SeeB又はIpaDである、請求項1に記載のワクチン。

[請求項3]
III型分泌システムのV抗原又はその相同体タンパク質がPcrVタンパク質である、請求項2に記載の病原性グラム陰性菌に対するワクチン。

[請求項4]
病原性グラム陰性菌が、緑膿菌、ペスト菌、百日咳菌、エルシニア菌、サルモネラ菌、赤痢菌、エアロモナスヒドロフィラ菌、せっそう病原因菌、仮性結核菌、病原性大腸菌、腸炎ビブリオ菌、ビブリオ・ハーベイ菌又はクラミジア菌である、請求項1~3のいずれか1項に記載のワクチン。

[請求項5]
病原性グラム陰性菌が緑膿菌である、請求項4に記載のワクチン。

[請求項6]
CpG ODNが、ホスホロチオエート骨格を有するものである、請求項1~5のいずれか1項に記載のワクチン。

[請求項7]
CpG ODNのクラスが、A class(D type)、B class(K type)、C class又はP classである、請求項1~6のいずれか1項に記載のワクチン。

[請求項8]
CpG ODNのクラスがB class(K type)である、請求項7に記載のワクチン。

[請求項9]
アジュバントがCpG(K3)、CpG(D35)、CpG ODN(1018 ISS)及びCpG 7909からなる群から選ばれる少なくとも1種である、請求項1~8のいずれか1項に記載の病原性グラム陰性菌に対するワクチン。

[請求項10]
アジュバントがCpG(K3)である、請求項9に記載の病原性グラム陰性菌に対するワクチン。

[請求項11]
経鼻投与または吸入投与される、請求項1~10のいずれか1項に記載の病原性グラム陰性菌に対するワクチン。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KYOTO PREFECTURAL PUBLIC UNIVERSITY CORPORATION
  • National Institutes of Biomedical Innovation, Health and Nutrition
  • Inventor
  • SAWA, Teiji
  • ISHII, Ken
  • HAMAOKA, Saeko
  • NAITO, Yoshifumi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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