KR970707281A - 풀리뉴클레오티드 결핵 백신(A polynucleotide tuberculosis vaccine) - Google Patents

풀리뉴클레오티드 결핵 백신(A polynucleotide tuberculosis vaccine)

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KR970707281A
KR970707281A KR1019970703204A KR19970703204A KR970707281A KR 970707281 A KR970707281 A KR 970707281A KR 1019970703204 A KR1019970703204 A KR 1019970703204A KR 19970703204 A KR19970703204 A KR 19970703204A KR 970707281 A KR970707281 A KR 970707281A
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functional equivalents
mycobacterial
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mycobacterium tuberculosis
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마가렛 에이 리우
도나 몽고메리
제프리 울머
쟝 콘텐트
크리스 휴젠
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폴락 도나 엘
머크 앤드 캄파니, 인코포레이티드
호이베르스빈 하 반
엔. 브이. 이노제네틱스 에스. 에이.
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Publication of KR970707281A publication Critical patent/KR970707281A/ko

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Abstract

미코박테이움 튜베르쿨로시스(M.tb) 단백질을 암호화하는 유전자를 진핵성 발현 백터내로 클로닝시켜 암호화된 단백질을 포유동물 근육 세포에서 생체내 발현시킨다. 폴리뉴클레이티드 백신 또는 PNV로 불리우는 상기 DNA 작제물을 동물의 근육내로 주사하여 상기 동물을 면역화시킨다. M.tb 항원에 대한 면역 항혈청이 생성된다. 특이적 T-세포 반응이 백신 처리시킨 마우스의 비장 세포에서 검정되었으며 항원(85)에 반응하는 사이토킨 분비 프로필은 Th1 유형의 헬퍼 T-세포 반응(즉, 고 IL-2 및 IFN-γ)을 나타낸다. M.tb DNA 백신의 보호 효능은 대조군 DNA-백신처리시킨 마우스 또는 이러한 백신처리가 이루어지지 않은 마우스에서의 1차 감염에 비하여, M.tb DNA 백신처리시킨 마우스의 비장 및 폐에서의 미코박테리아성 증가의 감소로 측정된 바와 같이, 엠. 보비스 BCG로의 챌린지 후의 마우스에서 입증되었다.

Description

풀리뉴클레오티드 결핵 백신(A polynucleotide tuberculosis vaccine)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 M.tb 유전자를 발현 백터내로 클로닝하는 일반적인 원리를 나타낸 것이다. 제2도는 V1Jns. tPA85A. C1의 벡터 지도를 나타낸 것이다, 제3도는 V1Jns. 85A. C2의 벡터 지도를 나타낸 것이다, 제7도는 작제물의 N-말단 서열 검증을 나타낸 것이다., 제10도는 Tb DNA 백신에 의한 BALB/c 마우스에서의 1L-2의 생성을 도시한 것이다.

Claims (22)

  1. 하나 이상의 미코박테리아 단백질 또는 이의 작용성 등가물을 암호화하고 전사 프로모터에 작동적으로 연결된 유전자 하나 이상을 포함하는, 척추동물 조직내로의 도입시 항체, CTL, 헬퍼 T 임파구 반응 및 보호 면역 반응 중에서 선택된 하나 이상의 항-미코박테리아성 면역 반응을 유도하는 폴리뉴클레오티드.
  2. 제1항에 있어서, 유전자가 미코박테리움 튜베르쿨로시스(Mycobacterium tuberculosis) 단백질 및 이의 작용성 등가물을 암호화하는 폴리뉴클레오티드.
  3. 제2항에 있어서, 유전자가 항원 85A, B 및/또는 C로 이루어진 그룹중에서 선택된 단백질, 및 이의 작용성 등가물을 암호화하는 폴리뉴클레오티드.
  4. 제1항에 따른 폴리뉴클레오티드 1ng 내지 5㎎을 척추동물의 조직내로 도입시킴을 포함하여, 척주동물에서 미코박테리아성 에피토프에 대한 면역 반응을 유도하는 방법.
  5. 제4항에 있어서, 유전자가 미코박테리움 튜베르쿨로시스 단백질 및 이의 작용성 등가물을 암호화하는 방법.
  6. 제5항에 있어서, 유전자가 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 단백질, 및 이의 작용성 등가물을 암호화하는 방법.
  7. 제1항에 따른 폴리뉴클레오티드와 약제학적으로 허용되는 담체를 포함하는 미코박테리아성 항원에 대한 면역 반응을 유도하기 위한 백신.
  8. 제7항에 있어서, 항원이 미코박테리움 튜베르쿨로시스 항원, 및 이의 작용성 등가물인 백신.
  9. 제8항에 있어서, 항원이 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 단백질, 및 이의 작용성 등가물인 백신.
  10. 미코박테리아성 감염을 억제시키고/시키거나 미코박테리아성 질병을 완화시켜 주는 면역 반응을 유발시키는, 분리되어 정제된 미코박테리아 유전자 하나 이상을 척추동물의 조직내로 도입함을 포함하여, 미코박테리아성 항원에 대한 면역 반응을 유도하는 방법.
  11. 제10항에 있어서, 유전자가 미코박테리움 튜베르쿨로시스 단백질 및 이의 작용성 등가물을 암호화하는 방법.
  12. 제11항에 있어서, 유전자가 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 단백질, 및 이의 작용성 등가물을 암호화하는 방법.
  13. a) 진핵성 전사 프로모터; b) 하나 이상의 미코박테리아성 에피토프를 암호화하는 상기 프로모터, 및 해독 말단화 시그날에 작동적으로 연결된 개방 판독 프레임; 및 c) 임의로, 하나 이상의 작동적으로 연결된 IRES, 하나 이상의 부가의 유전자를 암호화하는 하나 이상의 개방 판독 프레임 및 하나 이상의 전사 말단화 시그날을 포함하는 폴리뉴클레오티드.
  14. 제13항에 있어서, c)의 부가의 유전자가 CM-CSF, IL-12, 인터페론, 및 T-세포 공동자극성 단백질의 B7계의 구성원으로 이루어진 그룹중에서 선택된 면역조절성 또는 면역자극성 유전자인 폴리뉴클레오티드.
  15. 제13항에 있어서, a)의 미코박테리아 유전자가 미코박테리움 튜베르쿨로시스 단백질 및 이의 작용성 등가물을 암호화하는 폴리뉴클레오티드.
  16. 제15항에 있어서, a)의 미코박테리아 유전자가 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 미코박테리움 튜베르쿨로시스 단백질 및 이의 작용성 등가물을 암호화하는 폴리뉴클레오티드.
  17. 제13항에 있어서, c)의 부가의 유전자가 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 미코박테리움 튜베르쿨로시스 유전자 및 이의 작용성 등가물인 폴리뉴클레오티드.
  18. 하나 이상의 미코박테이아성 단백질 또는 이의 작용성 등가물을 암호화하고 전사 프로모터에 작동적으로 연결된 유전자를 포함하여 척추동물 조직내로의 도입시 항체, CTL, 헬퍼 T 임파구 반응 및 보호 면역 반응 중에서 선택된 항-미코박테리아성 면역 반응을 유도시키는 폴리뉴클레오티드를 사용하여, 이러한 치료를 필요로 하는 환자를 치료하는 방법.
  19. 제18항에 있어서, 유전자가 미코박테리움 튜베르쿨로시스 단백질 및 이의 작용성 등가물을 암호화하는 방법.
  20. 제19항에 있어서, 유전자가 항원 85A, B 및 C로 이루어진 그룹중에서 선택된 하나 이상의 단백질, 및 이의 작용성 등가물을 암호화하는 방법.
  21. 제10항에 있어서, 환자가 사육 동물 또는 가축인 방법.
  22. 제1항에 따른 폴리뉴클레오티드와 약제학적으로 허용되는 담체를 포함하는, 가축 또는 농작용 동물에서 미코박테리아성 감염에 대한 면역 반응을 유도하기 위한 백신.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019970703204A 1994-11-14 1995-11-13 풀리뉴클레오티드 결핵 백신(A polynucleotide tuberculosis vaccine) KR970707281A (ko)

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US08/338,992 US5736524A (en) 1994-11-14 1994-11-14 Polynucleotide tuberculosis vaccine
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