KR950704492A - CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS - Google Patents

CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS

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KR950704492A
KR950704492A KR1019950701811A KR19950701811A KR950704492A KR 950704492 A KR950704492 A KR 950704492A KR 1019950701811 A KR1019950701811 A KR 1019950701811A KR 19950701811 A KR19950701811 A KR 19950701811A KR 950704492 A KR950704492 A KR 950704492A
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제임스 엘. 미첼
데니스 엘. 카스퍼
프레드릭 엠. 오수벨
로렌스 씨. 마도프
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데이비드 제이. 글래스
더 제네랄 하스피탈 코오포레이션
쉘비 캘버트 오스
브리검 앤드 우먼즈 하스피탈
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Abstract

본 발명은 비(B)군 연쇄상구균에 의해 초래되는 감염으로부터 수용체를 방어할 수 있는 백신에 관한 것이다, 상기 백신은 다당류-단백질 부분을 제공하고, (a)비(B)군 연쇄상구균 다당류를 포함하며, 이때 상기 다당류가 (b)비(B)군 연쇄상구균에 대한 방어 항체를 유도할 수 있는 능력을 보유하는 비(B)군 연쇄상구균 C 단백질 알파 항원의 기능적 유도체에 접합된다, 상기 백신은 이러한 다당류 단백질 유니트와 한가지 유형만을 포함할 수 있거나 유니트의 한가지 이상 유형의 혼합물을 포함할 수 있다,The present invention relates to a vaccine capable of protecting a receptor from infection caused by non-B group streptococci, said vaccine providing a polysaccharide-protein moiety and comprising (a) a non-B group streptococcal polysaccharide. Wherein said polysaccharide is conjugated to a functional derivative of a non-B group streptococcal C protein alpha antigen that possesses the ability to induce a protective antibody against (b) non-B group streptococci. May comprise only one type of these polysaccharide protein units or may comprise a mixture of one or more types of units,

Description

비(B)군 연쇄상구균에 대한 접합 백신(CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS)CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is an open matter, no full text was included.

제1도는 플라즈미드 pUX12를 제조하기 위한 pUC12의 변형을 도시한다,1 shows a modification of pUC12 to prepare plasmid pUX12,

제2도는 플라즈미드 pUX12의 제한 및 전사지도를 도시한다,2 shows the restriction and transcription map of plasmid pUX12,

제3도는 +1리딩 프레임 플라즈미드 pUX12+1(A), -1 리딩 프레임 플라즈미드 pUX12-1(C)를 제조하기 위해 pUX12에 향한 변형을 도시한다, (B)는 -1리딩 프레임 플라즈미드를 추가로 형성할 수 있는 구성을 도시한다,3 shows a modification towards pUX12 to prepare +1 leading frame plasmid pUX12 + 1 (A), -1 leading frame plasmid pUX12-1 (C), (B) further adding -1 leading frame plasmid Shows a configuration that can be formed,

Claims (27)

(a)군-특이성 또는 유형-특이성 비(B)군 연쇄상구균 다당류를 포함하는 디(B)군 연쇄상구균에 의한 감염에 대해 숙주 면역성을 부여할 수 있는 접합 백산으로서, 상기 다당류는 (b)비 (B)군 연쇄상구균 C단백질 알파항원의 기능적 유도체에 접합되어 있고, 상기 유도체가 상기 비(B)군 연쇄상구균에 대한 방어 항체를 유도할 수 있는 접합 백신.(a) a conjugated white acid capable of conferring host immunity against infection by di (B) group streptococci comprising group-specific or type-specific ratio (B) group streptococcal polysaccharides, wherein the polysaccharide is (b) A conjugated vaccine conjugated to a functional derivative of a non-B group streptococcal C protein alpha antigen, said derivative capable of inducing a protective antibody against said non-B group streptococci. 제1항에 있어서, 다당류가 협막 다당류인 접한 백신.The vaccine of claim 1, wherein the polysaccharide is a capsular polysaccharide. 제1항에 있어서, C단백질 알파 항원 유도체가 N, C, N-C, R1, R2, R3, R4, R5, R6, R7, R8, R9, N-R1, N-R2, N-R3, N-R4, N-R5, N-R6, N-R6, N-R7, N-R8, N-R9, R1-C, R2-C, R3-C, R4-C, R5-C, R6-C, R7-C, R8-C, R9-C, N-R1-C, N-R2-C, N-R3-C, N-R4-C, N-R5-C, N-R6-C, N-R7-C, N-R8-C 및 N-R9-C로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 백신으로서, 이때 "N"이 시그날 서열 존재 또는 부재하에서 제6도에 도시한 서열내에서 발견되는 5'아미노산 측부 서열이고, "C"가 제6도에 도시한 바와 같이 48 아미노산 C-말단 앵커 서열이고, "R"이 제6도의 DNA 서열의 679번째 아미노산에 존재하는 82 아미노산 반복 서열의 1개의 카피이며, "Rx"가 인접하는 R 유니트의 아미노 말단에 대한 1개의 R 유니트의 카르복실 말단에 직렬로 연결된, 이 반복 서열의 직렬 카피의 "X"수인 접합 백신.The method of claim 1, wherein the C protein alpha antigen derivative is N, C, NC, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , NR 1 , NR 2 , NR 3 , NR 4 , NR 5 , NR 6 , NR 6 , NR 7 , NR 8 , NR 9 , R 1 -C, R 2 -C, R 3 -C, R 4 -C, R 5 -C, R 6 -C, R 7 -C, R 8 -C, R 9 -C, NR 1 -C, NR 2 -C, NR 3 -C, NR 4 -C, NR 5 -C, NR 6 -C, A conjugate vaccine selected from one or more members of the group consisting of NR 7 -C, NR 8 -C and NR 9 -C, wherein "N" is present in the sequence shown in FIG. 6 with or without the signal sequence. 82 amino acid repeat sequence found 5 'amino acid flanking sequence, "C" is a 48 amino acid C-terminal anchor sequence as shown in Figure 6, and "R" is present at the 679th amino acid of the DNA sequence of Figure 6 A conjugate vaccine, wherein one copy of is a "X" number of serial copies of this repeat sequence wherein "Rx" is connected in series to the carboxyl terminus of one R unit relative to the amino terminus of the adjacent R unit. 제3항에 있어서, 유도체가 N, C, R1, R2, R3, R4, R5, R6, R7, R8및 R9로 구성되는 군의 1개 이상의 구성원으로 부터 선택되는 접합 백신.The compound of claim 3, wherein the derivative is selected from one or more members of the group consisting of N, C, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 Conjugate vaccine. 제4항에 있어서, 유도체가 N, C, R1, R2, R3, R4, R5, R6, R7, R8및 R9로 구성되는 군의 1개 이상의 구성원으로 부터 선택되는 접합 백신.The method of claim 4, wherein the derivative is selected from one or more members of the group consisting of N, C, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 Conjugate vaccine. 제3항에 있어서, 유도체가 N-C, N-R1, N-R2, N-R3, N-R4, N-R5, N-R6, N-R7, N-R8및 N-R9로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 백신.The conjugate vaccine of claim 3, wherein the derivative is selected from one or more members of the group consisting of NC, NR 1 , NR 2 , NR 3 , NR 4 , NR 5 , NR 6 , NR 7 , NR 8 and NR 9 . . 제6항에 있어서, 유도체가 N-C, N-R1, N-R2, N-R3, N-R4, N-R5, N-R6, N-R7, N-R8및 N-R9로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 백신.The conjugate vaccine of claim 6, wherein the derivative is selected from one or more members of the group consisting of NC, NR 1 , NR 2 , NR 3 , NR 4 , NR 5 , NR 6 , NR 7 , NR 8 and NR 9 . . 제3항에 있어서, 유도체가 R1-C, R2-C, R3-C, R4-C, R5-C, R6-C, R7-C, R8-C 및 R9-C로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 벡신.The compound of claim 3, wherein the derivative is R 1 -C, R 2 -C, R 3 -C, R 4 -C, R 5 -C, R 6 -C, R 7 -C, R 8 -C and R 9 A conjugated bexin selected from one or more members of the group consisting of -C. 제8항에 있어서, 유도체가 R1-C, R2-C, R3-C, R4-C, R5-C, R6-C, R7-C, R8-C 및 R9-C로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 벡신.The compound of claim 8, wherein the derivative is R 1 -C, R 2 -C, R 3 -C, R 4 -C, R 5 -C, R 6 -C, R 7 -C, R 8 -C and R 9 A conjugated bexin selected from one or more members of the group consisting of -C. 제3항에 있어서, 유도체가 N-R1-C, N-R2-C, N-R3-C, N-R4-C, N-R5-C, N-R6-C, N-R7-C, N-R8-C 및 N-R9-C로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 백신.The derivative of claim 3 wherein the derivative is NR 1 -C, NR 2 -C, NR 3 -C, NR 4 -C, NR 5 -C, NR 6 -C, NR 7 -C, NR 8 -C and NR 9 A conjugate vaccine selected from one or more members of the group consisting of -C. 제10항에 있어서, 유도체가 N-R1-C, N-R2-C, N-R3-C, N-R4-C, N-R5-C, N-R6-C, N-R7-C, N-R8-C 및 N-R9-C로 구성되는 군의 1개 이상의 구성원으로부터 선택되는 접합 백신.The derivative of claim 10 wherein the derivative is NR 1 -C, NR 2 -C, NR 3 -C, NR 4 -C, NR 5 -C, NR 6 -C, NR 7 -C, NR 8 -C and NR 9 A conjugate vaccine selected from one or more members of the group consisting of -C. 비(B)군 연쇄상구균 알파 항원의 유도체를 암호화하는 유전자 서열을 포함하는 재조합 분자로서, 이때 유전자가 비(B)군 연쇄상구균에 대한 방어항체를 유도할 수 있는 재조합 분자.A recombinant molecule comprising a gene sequence encoding a derivative of a non-B streptococcal alpha antigen, wherein the gene is capable of inducing a protective antibody against non-B streptococcus. 제12항에 있어서, N, C, N-C, R1, R2, R3, R4, R5, R6, R7, R8, R9, N-R1, N-R2, N-R3, N-R4, N-R5, N-R6, N-R7, N-R8, N-R9, R1-C, R2-C, R3-C, R4-C, R5-C, R6-C, R7-C, R8-C, R9-C, N-R1-C, N-R2-C, N-R3-C, N-R4-C, N-R5-C, N-R6-C, N-R7-C, N-R8-C 및 N-R9-C로 구성되는 군으로부터 선택되는 재조합 분자.The method of claim 12, wherein N, C, NC, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , NR 1 , NR 2 , NR 3 , NR 4 , NR 5 , NR 6 , NR 7 , NR 8 , NR 9 , R 1 -C, R 2 -C, R 3 -C, R 4 -C, R 5 -C, R 6 -C, R 7 -C , R 8 -C, R 9 -C, NR 1 -C, NR 2 -C, NR 3 -C, NR 4 -C, NR 5 -C, NR 6 -C, NR 7 -C, NR 8 -C And NR 9 -C. 제13항에 있어서, 유도체가 N, C, N-C, R1, R2, R3, R4, R5, R6, R7, R8및 R9로 구성되는 군으로부터 선택되는 재조합 분자.The recombinant molecule of claim 13, wherein the derivative is selected from the group consisting of N, C, NC, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 . 제13항에 있어서, N-R1, N-R2, N-R3, N-R4, N-R5, N-R6, N-R7, N-R8및 N-R9로 구성되는 군으로부터 선택되는 재조합 분자.The recombinant molecule of claim 13, wherein the recombinant molecule is selected from the group consisting of NR 1 , NR 2 , NR 3 , NR 4 , NR 5 , NR 6 , NR 7 , NR 8 and NR 9 . 제13항에 있어서, 유도체가 R1-C, R2-C, R3-C, R4-C, R5-C, R6-C, R7-C, R8-C 및 R9-C로 구성되는 군으로부터 선택도는 재조합 분자.The compound of claim 13, wherein the derivative is R 1 -C, R 2 -C, R 3 -C, R 4 -C, R 5 -C, R 6 -C, R 7 -C, R 8 -C and R 9 Selectivity from the group consisting of -C is a recombinant molecule. 제 13항에 있어서, N-R1-C, N-R2-C, N-R3-C, N-R4-C, N-R5-C, N-R6-C, N-R7-C, N-R8-C 및 N-R9-C로 구성되는 군으로부터 선택되는 재조합 분자.The method of claim 13, wherein NR 1 -C, NR 2 -C, NR 3 -C, NR 4 -C, NR 5 -C, NR 6 -C, NR 7 -C, NR 8 -C and NR 9 -C Recombinant molecule selected from the group consisting of. 제12항 내지 제17항중 어느 한 항에 있어서, 상기 분자가 박테리아내에서 상기 C 단백질 알파 항원을 발현한 수 있는 재조합 분자.The recombinant molecule of claim 12, wherein the molecule is capable of expressing the C protein alpha antigen in bacteria. 제18항의 재조합 분자를 포함하는 재조합 백터.A recombinant vector comprising the recombinant molecule of claim 18. 제19항에 있어서, 벡터가 플라즈미드, 코스미드, 트랜스포존 및 파지로 구성되는 군으로부터 선택되는 재조합 벡터.The recombinant vector of claim 19, wherein the vector is selected from the group consisting of plasmid, cosmid, transposon, and phage. 제18항의 재조합 분자를 사용하여 형질전환된 숙주 세포.A host cell transformed using the recombinant molecule of claim 18. 제21항에 있어서, 숙주 세포가 박테리아 세포 및 효모 세포로 부터 선택되는 숙주 세포.The host cell of claim 21, wherein the host cell is selected from bacterial cells and yeast cells. 제22항에 있어서, 박테리아 세포가 비(B)군 연쇄상구균인 숙주 세포.23. The host cell of claim 22, wherein the bacterial cell is a non-B group streptococci. 제22항에 있어서, 박테리아 세포가 에스케리치아 콜리인 숙주 세포.The host cell of claim 22, wherein the bacterial cell is Escherichia coli. 비(B)군 연쇄상구균에 의해 초래되는 감염의 위험에 처한 것이라 여겨지는 개체에 상기 감염에 대한 숙주 면역성을 부여할 수 있는 접합 백시의 유효량을 투여함을 포함하여, 상기 감염을 예방 또는 감독화하는 방법으로서, 상기 백신은 (a)비(B)군 연쇄상구균 다당류를 포함하며, 이때 상기 다당류는 (b)기능적 C단백질 알파 항원 유도체에 접합되는 방법.Preventing or supervising the infection, including administering to a subject believed to be at risk of infection caused by non-B group streptococci, an effective amount of conjugated vaccinia capable of conferring host immunity to the infection. Wherein said vaccine comprises (a) a non-B group streptococcal polysaccharide, wherein said polysaccharide is conjugated to (b) a functional C protein alpha antigen derivative. 여성의 태아에 대한 비(B)군 연쇄상구균에 의해 초래되는 감염에 대한 면역성을 부여할 수 있는 접합 백신의 유효량을 여성에게 투여함을 포함하여, 상기 감염을 예방 또는 감독화하는 방법으로서, 상기 백신은 (a)비(B)군 연쇄상구균 다당류를 포함하며, 이때 상기 다당류는 (b)기능적 C단백질 알파 항원 유도체에 접합되는 방법.A method of preventing or supervising an infection comprising administering to a woman an effective amount of a conjugated vaccine capable of conferring immunity to an infection caused by a non-group B streptococcus against a fetus of a woman, comprising: The vaccine comprises (a) a non-B group streptococcal polysaccharide, wherein the polysaccharide is conjugated to (b) a functional C protein alpha antigen derivative. 비(B)군 연쇄상구균에 의해 초래되는 감염에 대한 숙주 면역성을 부여할 수 있는 접합 백신에 대한 제2개체의 노출로부터 유도된 항혈청의 유효량을 이러한 감염의 위험에 처한 것이라 여겨지는 개체에게 투여함을 포함하여, 상기 감염을 예방 또는 감독화하는 방법으로서, 상기 백신은 (a)비(B)군 연쇄상구군 다당류를 포함하며, 이때 상기 다당류가 (b)C단백질 알파항원 유도체에 접합되는 방법.An effective amount of antiserum derived from exposure of a second individual to a conjugate vaccine that can confer host immunity against infections caused by non-B group streptococci is administered to the individual considered to be at risk of such infection. A method for preventing or supervising the infection, comprising: (a) a non- (B) group serial group polysaccharide, wherein the polysaccharide is conjugated to (b) C protein alpha antigen derivative. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
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