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1. WO2013011942 - MUTANT CANINE MADNESS VIRUS AND VACCINE

Publication Number WO/2013/011942
Publication Date 24.01.2013
International Application No. PCT/JP2012/067927
International Filing Date 13.07.2012
IPC
C12N 7/04 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
7Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
04Inactivation or attenuation; Producing viral sub-units
A61K 39/205 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
12Viral antigens
205Rhabdoviridae, e.g. rabies virus
A61P 31/12 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
31Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
12Antivirals
C12N 15/09 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
CPC
A61K 2039/5254
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
51comprising whole cells, viruses or DNA/RNA
525Virus
5254avirulent or attenuated
A61K 39/12
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
12Viral antigens
A61P 31/12
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
31Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
12Antivirals
C07K 14/005
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
005from viruses
C12N 2760/20122
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2760ssRNA Viruses negative-sense
00011ssRNA Viruses negative-sense
20011Rhabdoviridae
20111Lyssavirus, e.g. rabies virus
20122New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
C12N 2760/20134
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2760ssRNA Viruses negative-sense
00011ssRNA Viruses negative-sense
20011Rhabdoviridae
20111Lyssavirus, e.g. rabies virus
20134Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Applicants
  • 国立大学法人岐阜大学 GIFU UNIVERSITY [JP]/[JP] (AllExceptUS)
  • 共立製薬株式会社 KYORITSU SEIYAKU CORPORATION [JP]/[JP] (AllExceptUS)
  • 伊藤 直人 ITO Naoto [JP]/[JP] (UsOnly)
  • 杉山 誠 SUGIYAMA Makoto [JP]/[JP] (UsOnly)
Inventors
  • 伊藤 直人 ITO Naoto
  • 杉山 誠 SUGIYAMA Makoto
Agents
  • 丹羽 俊輔 NIWA Shunsuke
Priority Data
2011-15697315.07.2011JP
Publication Language Japanese (JA)
Filing Language Japanese (JA)
Designated States
Title
(EN) MUTANT CANINE MADNESS VIRUS AND VACCINE
(FR) VIRUS DE LA RAGE MUTANT ET VACCIN
(JA) 変異狂犬病ウイルス及びワクチン
Abstract
(EN)
[Problem] To provide a canine madness vaccine which is higly safe, effective and inexpensive. [Solution] Provided are: a mutant canine madness virus (e.g., strain ERA-N273/394-G333 shown in fig. 2) which has at least the following mutations in a structural protein of a canine madness virus, i.e., the mutation of the amino acid reside at position-273 in N protein into an amino acid residue other than phenylalanine, the mutations of the amino acid reside at position-394 in N protein into an amino acid residue other than tyrosine, and the mutation of the amino acid residue at position-333 in G protein into an amino acid residue other than arginine or lysine; a canine madness vaccine preparation containing the mutant canine madness virus; and others. The introduction of the mutation of the amino acid residue at position-333 in G protein induces the attenuation of the virulence of a canine madness virus, and the introduction of the mutations of the amino acid residues at position-273 and position-394 in N protein induces the improvement in immunogenicity and safety of the canine madness virus. In addition, the introduction of the mutations of the amino acid residues at position-273 and position-394 in N protein enables the prevention of the increase in the virulence of the canine madness virus even when the mutation of the amino acid residue at position-194 in G protein into lysine occurs and, as a result, the possibility of the occurrence of reversion of pathogenicity of the canine madness virus caused by mutation can be reduced and the safety of the canine madness virus can be further improved.
(FR)
[Problème] Produire un vaccin contre la rage qui est très sûr, efficace et économique. [Solution] La présente invention concerne : un virus de la rage mutant (par exemple, la souche ERA-N273/394-G333 représentée sur la figure 2) qui a au moins les mutations suivantes dans une protéine structurale d'un virus de la rage, c'est-à-dire, la mutation de l'acide aminé résidant à la position 273 dans la protéine N en un résidu d'acide aminé autre que la phénylalanine, les mutations de l'acide aminé situé à la position 394 dans la protéine N en un résidu d'acide aminé autre que la tyrosine, et la mutation du résidu d'acide aminé à la position 333 dans la protéine G en un résidu d'acide aminé autre que l'arginine ou la lysine ; une préparation de vaccin contre la rage contenant le virus de la rage mutant ; et d'autres. L'introduction de la mutation du résidu d'acide aminé à la position 333 dans la protéine G induit l'atténuation de la virulence d'un virus de la rage, et l'introduction des mutations des résidus d'acide aminé à la position 273 et la position 394 dans la protéine N induit l'amélioration de l'immunogénicité et la sécurité du virus de la rage. De plus, l'introduction des mutations des résidus d'acide aminé à la position 273 et la position 394 dans la protéine N permet la prévention de l'augmentation de la virulence du virus de la rage même lorsque la mutation du résidu d'acide aminé à la position 194 dans la protéine G en lysine se produit et, en conséquence, la possibilité de l'occurrence d'inversion de la pathogénicité du virus de la rage causée par une mutation peut être réduite et la sécurité du virus de la rage peut en outre être améliorée.
(JA)
 【課題】安全性が高く、効果的かつ安価な狂犬病ワクチンの提供。 【解決手段】狂犬病ウイルスの構造タンパク質中、少なくとも、Nタンパク質の273位がフェニルアラニン以外のアミノ酸、Nタンパク質の394位がチロシン以外のアミノ酸、Gタンパク質の333位がアルギニン又はリジン以外のアミノ酸である変異狂犬病ウイルス(例えば、図2中、ERA-N273/394-G333株)、これらの変異狂犬病ウイルスを含有する狂犬病ワクチン製剤などを提供する。Gタンパク質333位のアミノ酸の変異導入による狂犬病ウイルスの弱毒化に加え、Nタンパク質の273位及び394位のアミノ酸に変異導入することにより免疫原性及び安全性を向上できる。加えて、Nタンパク質の273位及び394位のアミノ酸に変異導入することにより、Gタンパク質の194位がリジンに変異した場合にも強毒化を防止できるため、突然変異による病原性復帰が起こる可能性を低減でき、安全性をより高めることができる。
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