KR20070094762A - 수막구균에 대한 백신 - Google Patents
수막구균에 대한 백신 Download PDFInfo
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- KR20070094762A KR20070094762A KR1020077015481A KR20077015481A KR20070094762A KR 20070094762 A KR20070094762 A KR 20070094762A KR 1020077015481 A KR1020077015481 A KR 1020077015481A KR 20077015481 A KR20077015481 A KR 20077015481A KR 20070094762 A KR20070094762 A KR 20070094762A
- Authority
- KR
- South Korea
- Prior art keywords
- ala
- leu
- gly
- glu
- thr
- Prior art date
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Abstract
백신에 유용한 다양한 폴리펩티드, 또는 이의 변이체 또는 단편 또는 상기의 융합체가 기재된다. 상기 폴리펩티드는 서열번호 (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68) 중의 임의의 하나로부터 선택된 아미노산 서열을 포함하는 폴리펩티드; 또는 이의 단편 또는 변이체 또는 상기 단편 또는 변이체의 융합체일 수 있으며, 수막구균에 대한 백신에 유용하다.
Description
본 발명은 백신 및 이의 용도, 특히 수막구균 질환에 관한 것이다.
본 명세서에 이전에 공개된 문헌의 열거 또는 논의는 상기 문헌이 반드시 당업계의 상태의 일부 또는 통상적인 일반 지식이라는 인식으로서 받아들여서는 안된다. 본 명세서에 열거된 문헌은 원용에 의해 본원에 포함된다.
미생물 감염은 특히 많은 병원성 미생물, 특히 박테리아가 항생제와 같은 항미생물제에 내성이거나 또는 내성이 될 수 있다는 사실의 면에서 인간 및 동물 건강에 심각한 위험으로 남아 있다.
예방접종은 미생물 감염과 싸우는 대안적인 접근을 제공하나, 병원성 미생물, 특히 유전학적으로 다양한 미생물의 상이한 분리주의 범위에 대해 효과적이고, 안전한 백신에 이용하기 위한 적절한 면역원을 동정하는 것은 종종 어렵다. 면역원으로서 실질적으로 본래의 미생물, 예를 들면 독성 결정 유전자에서 하나 또는 복수의 돌연변이를 전형적으로 포함하는 약독화된 살아있는 박테리아를 이용하는 백신을 개발하는 것이 가능하지만, 모든 미생물이 상기 접근에 잘 따르지 않으며, 안전성이 항상 보장될 수 없는 특정 미생물에 대해 상기 접근을 채택하는 것이 항상 바람직하지도 않다. 또한, 특정 미생물은 숙주 단백질을 흉내내는 분자를 발현 하며, 이는 백신에 바람직하지 못하다.
추가의 백신을 개발하는데 중요한 미생물의 특정 그룹은 접합체 혈청군 C 폴리사카라이드 백신의 도입에도 불구하고, 유럽, 북아메리카, 개발도상국 및 기타 지역에서 유아 사망률의 중요 원인으로 남아 있는 생명 위협 감염증인 수막구균 질환을 야기하는 수막구균 (Neisseria meningitidis)이다. 이는 α2-8 연결된 폴리시알산 캡슐을 발현하는 혈청군 B 균주 (NmB)에 의해 야기된 감염이 여전히 우세하기 때문이다. 수막구균에 관하여 용어 "혈청군"은 박테리아 상에 발현된 폴리사카라이드 캡슐을 말한다. 영국에서 야기 질환에서 가장 흔한 혈청군은 B인 반면, 아프리카에서는 A이다. 수막구균 패혈증은 높은 경우의 치명률을 전달하기를 계속하며; 생존자는 종종 주요한 심리학적 및/또는 신체적 장애가 남는다. 비특이적 전구 질환 후에, 수막구균 패혈증은 적당한 항미생물 치료 및 충분한 지지 대책에 불응하는 전격 질환으로서 나타날 수 있다. 그러므로, 수막구균 질환의 공중보건 위협과 싸우는 가장 최선의 접근은 예방 접종을 통해서이다.
수막구군 감염의 비특이적 초기 임상 징후 및 전격 코스는 치료가 종종 비효과적이라는 것을 의미한다. 그러므로, 예방접종이 상기 병원균에 의해 야기된 전세계의 질환 부담을 줄이는데 가장 효과적인 전략이라고 고려된다 (Feavers (2000) ABC of meningococcal diversity. Nature 404, 451-2). 혈청군 A, C, W135, 및 Y 수막구균 감염을 예방하기 위한 기존의 백신은 박테리아의 표면 상에 위치한 폴리사카라이드 캡슐에 기초한다 (Anderson et al (1994) Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun. 62, 3391-33955; Leach et al (1997) Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine. J Infect Dis. 175, 200-4; Lieberman et al (1996). Safety and immunogenicity of a serogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. A randomized controlled trial. J. American Med. Assoc. 275, 1499-1503). 혈청군 B 감염에 대한 백신에 대한 진전은 이의 캡슐인 α2-8 연결된 시알산의 단독중합체가 인간에서 비교적 불량한 면역원이므로 더욱 어렵다. 이는 인간 세포 부착 분자인 N-CAMl 상에 발현된 에피토프를 공유하기 때문이다 (Finne et al (1983) Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet 2, 355-357). 정말로, 혈청군 B 캡슐에 대한 면역 반응을 생성하는 것은 실질적으로 해로운 것으로 입증될 수 있다. 그리하여, 혈청군 B 수막구균 감염을 예방하기 위한 신규 백신에 대한 요구가 여전히 존재한다.
수막구균 질환에 대한 보호의 가장 입증된 면역 상관물은 혈청살균분석 (SBA)이다. SBA는 박테리아 세포 표면 상에 보체 침착, 막 공격 복합체의 어셈블리, 및 박테리아 용균을 매개하는 혈청 중의 항체 (통상 IgG2a 서브클래스)의 능력을 평가한다. SBA에서, 알려진 수의 박테리아가 지정된 보체 소스와 함께 혈청의 연속 희석액에 노출된다. 생존하는 박테리아의 수가 측정되며, SBA는 50% 사멸을 매개하는 혈청의 가장 높은 희석의 역수로서 정의된다. SBA는 혈청군 C 감염에 대 한 보호의 전조가 되며, NmB 감염에 대한 면역에 대한 대용물로서 널리 이용된다. 중요하게도, SBA는 백신의 임상 전 평가에 대한 면역의 준비된 마커이며, 임상 시험에서 적당한 종말점을 제공한다.
NmB 백신 개발에 대한 대부분의 노력은 효과적인 단백질 서브유닛을 규정하는데 향해 있다. 이종 항원으로서 발현되고, 동물에서 의미있는 반응을 생성하는 이의 능력에 대해 시험된 잠재적으로 표면 발현된 단백질에 대해 게놈 서열이 문의된 '역백신학 (Reverse vaccinology)'에 주요 투자가 있어 왔다. 그러나, 상기 접근은 1) 표면 발현된 항원을 예측하기 위한 컴퓨터 알고리즘, 2) 많은 잠재적인 면역원을 발현하지 못함, 및 3) 뮤린 면역 반응에 전반적인 의존에 의해 제한된다.
성공적인 백신에 대한 열쇠는 혈청군 또는 클론군과 무관하게 폭넓은 범위의 질환 분리주에 대한 보호를 유도하는 항원(들)을 규정하는 것이다. 유전자 스크리닝 방법 (면역원에 대한 유전자 스크리닝 또는 GSI라 명명함)을 미생물 균주의 유전적 다양성을 넘어서 보존되는 항원을 분리하기 위해 이용하였으며, 이는 수막구균 균주와 관련하여 예시된다. 이는 하기에 더욱 상세히 기재한 GSI에 의해 수막구균 항원과 같은 미생물 항원을 동정함으로써 수행되었으며; 재조합 항원에 의해 유도된 면역 반응의 기능을 평가하고, 항원의 보호 효능을 평가함으로써 입증되었다 (실시예 및 본원에 원용에 의해 포함된 PCT/GB2004/005441 (2005년 7월 5일에 WO 2005/060995로서 공개됨)를 참고). 본질적으로, 상기 GSI 방법은 미생물을 처리한 동물에서 어느 폴리펩티드가 면역 반응과 관련되는지의 미생물의 폴리펩티드의 동정 방법에 관한 것으로, 상기 방법은 (1) 미생물의 복수의 상이한 돌연변이체 를 제공하는 단계; (2) 항체가 돌연변이체 미생물에 결합한다면 상기 돌연변이체 미생물은 사멸되는 조건하에 복수의 돌연변이체 미생물과 미생물 또는 이의 부분에 대한 면역 반응이 상승된 동물 유래의 항체와 접촉시키는 단계; 단계 (2)의 생존하는 돌연변이체 미생물을 선발하는 단계; (4) 임의의 생존하는 돌연변이체 미생물에서 상기 돌연변이를 포함하는 유전자를 동정하는 단계; 및 (5) 상기 유전자에 의해 코딩되는 폴리펩티드를 동정하는 단계를 포함한다. 폴리펩티드가 동정되는 방식에 의해, 이는 항원 폴리펩티드와 매우 관련된다는 것을 인식할 것이다.
실시예에 의해 더욱 상세히 기재된 바와 같이, GSI 방법에 의해 동정된 특정 유전자는 수막구균의 NBM0341 (TspA), NMB0338, NMB1345, NMB0738, NBM0792 (NadC 패밀리), NMB0279, NMB2050, NMB1335 (CreA), NMB2035, NMB1351 (Fmu 및 Fmv), NMB1574 (IIvC), NMB1298 (rsuA), NMB1856 (LysR 패밀리), NMBO119, NMB1705 (rfak), NMB2065 (HemK), NMB0339, NMB0401 (putA), NMB 1467 (PPX), NMB2056, NMB0808, NMB0774 (upp), NMA0078, NMB0337 (분지쇄 아미노산 전달효소), NMB0191 (ParA 패밀리), NMB1710 (글루타메이트 탈수소효소 (gdhA), NMB0062 (rfbA-1), NMB1583 (HisB), NMB0377, NMB0264, NMB1333, NMB1036, NMBl176, NMB1359 및 NMB1138 유전자이다. 수막구균에 대한 게놈 서열은 예를 들면, The Institute of Genome Research (TIGR); www.tigr.org로부터 유용하다.
상기 유전자가 발명자가 인식하는 한, 서열결정된 게놈의 일부를 형성하지만, 이는 분리되지는 않았으며, 코딩하는 폴리펩티드가 제조되지 않았으며 (분리되지도 않았음), 코딩하는 폴리펩티드가 백신의 성분으로서 유용할 수 있다는 표시도 없다.
그리하여, 본 발명은 상기 및 실시예에서 분리된 유전자 및 변이체 및 단편 및 상기 변이체 및 단편의 융합체를 포함하며, 전술한 유전자가 코딩하는 폴리펩티드와 함께, 이의 변이체 및 단편, 및 상기 단편 및 변이체의 융합체를 포함한다. 변이체, 단편 및 융합체는 하기에 더욱 상세히 기재된다. 바람직하게는, 상기 제시된 유전자의 변이체, 단편 및 융합체는 수막구균에 대한 중화 항체를 야기하는 폴리펩티드를 코딩하는 것이다. 유사하게, 바람직하게는, 이의 서열이 상기 제시된 폴리펩티드의 변이체, 단편 및 융합체는 수막구균에 대한 중화 항체를 야기하는 것이다. 상기 중화 항체는 면역계를 갖는 임의의 동물, 예를 들면, 래트, 마우스 또는 토기에서 제조될 수 있다. 본 발명은 또한 이의 서열이 실시예에 제시된 폴리펩티드 (바람직하게는 분리된 코딩 영역) 또는 상기 변이체, 단편 또는 융합체를 코딩하는 분리된 폴리뉴클레오티드를 포함한다. 본 발명은 또한 상기 폴리뉴클레오티드를 포함하는 발현 벡터 및 상기 폴리뉴클레오티드 및 벡터를 포함하는 숙주 세포 (하기에 더욱 상세히 기재됨)를 포함한다. 실시예에 기재된 폴리펩티드는 본 발명의 방법에 의해 동정된 항원이다.
본 발명의 방법의 실시에 이용하기 위한 분자 생물학적 방법은 예를 들면, 본원에 원용에 의해 포함된 [Sambrook & Russell (2001) Molecular Cloning, a laboratory manual, third edition, Cold Spring Harbor laboratory Press, Cold Spring Harbor, New York]으로부터 당업계에 주지되어 있다.
상기 유전자의 변이체는 예를 들면, 다른 미생물 또는 상기 미생물의 다른 균주의 관련 유전자를 동정하고, 상기 유전자를 클로닝, 분리 또는 합성함으로써 제조될 수 있다. 전형적으로, 상기 유전자의 변이체는 상기 제시된 유전자와 적어도 70% 서열 동일성, 더욱 바람직하게는 적어도 85% 서열 동일성, 가장 바람직하게는 적어도 95% 서열 동일성을 갖는 것이다. 당연히, 치환, 결실 및 삽입이 허용될 수 있다. 하나의 핵산 서열 및 또 다른 핵산 서열 사이의 유사성의 정도는 위스콘신 대학교의 컴퓨터 그룹의 GAp 프로그램을 이용하여 측정될 수 있다.
상기 유전자의 변이체는 또한 상기 유전자와 스트린전트 조건하에 혼성화하는 것이다. "스트린전트"는 상기 유전자가 막 상에 고정화되고, 프로브 (이 경우에, 길이가 200 뉴클레오티드 이상)가 용액 중에 있으며, 고정화된 유전자/혼성화된 프로브가 65℃에서 10분 동안 0.1 x SSC에서 세척될 때 상기 유전자가 상기 프로브에 혼성화하는 것을 의미한다. SSC는 0.15 M NaCl/0.015 M Na 시트레이트이다.
예를 들면, 상기 총 유전자의 20% 또는 30% 또는 40% 또는 50% 또는 60% 또는 70% 또는 80% 또는 90%인 상기 유전자 (또는 상기 변이체 유전자)의 단편이 제조될 수 있다. 바람직한 단편은 상기 코딩 서열의 전부 또는 일부를 포함한다. 상기 변이체 및 단편은 기타 비관련된 폴리뉴클레오티드에 융합될 수 있다.
상기 폴리뉴클레오티드는, 면역원성이며 상기 유전자가 동정된 미생물을 처리한 동물 유래의 항체와 반응성인 폴리펩티드를 코딩한다.
상기 항원은 상기 동정된 유전자에 의해 코딩된 폴리펩티드일 수 있으며, 상기 폴리펩티드의 서열은 상기 유전자 서열로부터 용이하게 추론될 수 있다. 추가의 구현예에서, 상기 항원은 상기 동정된 폴리펩티드의 단편 또는 상기 동정된 폴리펩티드의 변이체 또는 상기 폴리펩티드 또는 단편 또는 변이체의 융합체일 수 있다.
그리하여, 본 발명의 특정 양태는 서열번호 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68 중의 어느 하나로부터 선택된 아미노산 서열을 포함하는 폴리펩티드; 또는 이의 단편 또는 변이체 또는 상기 단편 또는 변이체의 융합체를 제공한다. 그리하여, 본 발명은 하기 분리된 단백질, 또는 이의 단편 또는 변이체, 또는 이의 융합체를 제공한다: NMB0341, NMB1583, NMB1345, NMB0738, NMB0792, NMB0279, NMB2050, NMB1335, NMB2035, NMB1351, NMB1574, NMB1298, NMB1856, NMB0119, NMB1705, NMB2065, NMB0339, NMB0401, NMB1467, NMB2056, NMB0808, NMB0774, NMA0078, NMB0337, NMB0191, NMB1710, NMB0062, NMB1333, NMB0377, NMB0264, NMB1036, NMB1176, NMB1359 및 NMB 1138.
예를 들면, 총 폴리펩티드의 20% 또는 30% 또는 40 % 또는 50% 또는 60% 또는 70% 또는 80% 또는 90%인 상기 동정된 폴리펩티드의 단편이 제조될 수 있다. 전형적으로, 단편은 적어도 10, 15, 20, 30, 40 , 50, 100개 이상의 아미노산이나, 500, 400, 300 또는 200개 아미노산 미만이다. 상기 폴리펩티드의 변이체가 제조될 수 있다. "변이체"는 삽입, 결실 및 보존적 또는 비보조적인 치환을 포함하는데, 상기 변화는 실질적으로 상기 단백질의 정상적인 기능을 변경하지 않는다. "보존적 치환"은 GIy, Ala; VaI, Ile, Leu; Asp, GIu; Asn, GIn; Ser, Thr; Lys, Arg; 및 Phe, Tyr과 같은 조합을 의도한다. 상기 변이체는 단백질 공학 및 자리 지정 돌연변이유발의 주지된 방법을 이용하여 제조될 수 있다.
변이체의 특정 부류는 예를 들면 관련 미생물 또는 상기 미생물의 다른 균주 유래의 상기 논의된 변이체 유전자에 의해 코딩된 것이다. 전형적으로, 상기 변이체 폴리펩티드는 본 발명의 방법을 이용하여 동정된 상기 폴리펩티드와 적어도 70% 서열 동일성, 더욱 바람직하게는 적어도 85% 서열 동일성, 가장 바람직하게는 적어도 95% 서열 동일성을 가진다.
2개의 폴리펩티드 사이의 퍼센트 서열 동일성은 적당한 컴퓨터 프로그램, 예를 들면 위스콘신 대학교의 유전 컴퓨터 그룹의 GAP 프로그램을 이용하여 결정될 수 있으며, 퍼센트 동일성은 이의 서열이 최적으로 정렬된 폴리펩티드에 관하여 계산된다는 것을 인식할 것이다.
상기 정렬은 대안적으로 Clustal W 프로그램을 이용하여 수행될 수 있다 (Thompson et al, (1994) Nucleic Acids Res 22, 4673-80). 상기 이용된 파라미터는 하기와 같다:
Fast pairwise 정렬 파라미터: K-tuple(word) 크기; 1, 윈도 크기; 5, 갭 페널티; 3, number of top diagonals; 5. 스코어링 방법: x 퍼센트.
다중 정렬 파라미터: 갭 오픈 페널티; 10, 갭 연장 패널티; 0.05. 스코어링 매트릭스: BLOSUM.
상기 융합체는 임의의 적당한 폴리펩티드를 갖는 융합체일 수 있다. 전형적으로, 상기 폴리펩티드는 융합된 폴리펩티드에 대한 면역 반응을 증진시킬 수 있는 것이다. 상기 융합체 파트너는 예를 들면, 친화성 크로마토그래피 칼럼에 고정될 수 있는 모이어티에 대한 결합 자리를 구성함으로써 정제를 용이하게 하는 폴리펩티드일 수 있다. 그리하여, 상기 융합체 파트너는 코발트 또는 니켈 이온에 결합하는 올리고-히스티딘 또는 기타 아미노산을 포함할 수 있다. 이는 또한 Myc 에피토프와 같은 단클론 항체에 대한 에피토프일 수 있다.
전술한 바와 같이, 상기 변이체 폴리펩티드 또는 폴리펩티드 단편, 또는 이의 융합체는 전형적으로 수막구균에 대한 중화 항체을 야기하는 것이다.
그러므로, 본 발명은 또한 전술한 항원을 제조하는 방법, 및 상기 방법에 해 수득가능하거나 또는 수득된 항원을 포함한다.
본 발명의 폴리뉴클레오티드는 당업계에 주지된 발현 벡터와 같은 벡터 내로 클로닝될 수 있다. 상기 벡터는 박테리아, 효모, 포유류 및 곤충 숙주 세포와 같은 숙주 세포에 존재할 수 있다. 본 발명의 항원은 적당한 숙주 세포에서 폴리뉴클레오티드로부터 용이하게 발현될 수 있으며, 백신에 이용하기 위해 이로부터 분리될 수 있다.
전형적인 발현 시스템은 시판되는 pET 발현 벡터 시리즈 및 BL21과 같은 대장균 숙주 세포를 포함한다. 발현된 폴리펩티드는 당업계에 공지된 임의의 방법에 의해 정제될 수 있다. 편리하게, 상기 항원은 전술한 친화성 칼럼에 결합하는 융합체 파트너에 융합되며, 상기 융합체는 친화성 칼럼 (예를 들면, 니켈 또는 코발트 친화성 칼럼)을 이용하여 정제된다.
상기 항원 또는 상기 항원을 코딩하는 폴리뉴클레오티드 (예를 들면, DNA 분자)는 백신에 이용하기에 특히 적합하다는 것을 인식할 것이다. 상기 경우에, 상기 항원은 그 속에서 생산된 숙주 세포로부터 정제된다 (또는 펩티드 합성에 의해 생산된다면, 합성의 임의의 오염물질로부터 정제된다). 전형적으로 상기 항원은 백신에 이용하기 위해 제형화되기 전에, 5% 미만의 오염 물질, 바람직하게는 2%, 1%, 0.5%, 0.1%, 0.01% 미만의 오염 물질을 포함한다. 상기 항원은 바람직하게는 실질적으로 발열원이 없다. 그리하여, 본 발명은 추가로 상기 항원을 포함하는 백신, 및 상기 항원과 인산완충염수와 같은 적당한 담체를 조합하는 것을 포함하는 백신의 제조 방법을 포함한다. 본 발명의 항원을 단독으로 투여하는 것이 가능하지만, 하나 이상의 허용가능한 담체와 함께 약학 제형물로서 제공하는 것이 바람직하다. 상기 담체(들)은 본 발명의 항원과 상용성인 면에서 "허용가능해야"하고, 이의 수용체에 해로워서는 안 된다. 전형적으로, 상기 담체는 멸균 및 발열원이 없는 물 또는 염수일 것이다.
상기 백신은 또한 편리하게 보조제를 포함할 수 있다. 환자의 활성 면역이 바람직하다. 상기 접근에서, 하나 이상의 항원이 적당한 보조제 및 담체를 포함하는 면역원성 제형물로 제조되며, 공지된 방식으로 환자에게 투여된다. 적당한 보조제는 프로인트 완전 또는 불완전 보조제, 뮤라밀 디펩티드, EP 109942, EP 180564 및 EP 231039의 "Iscoms", 수산화알루미늄, 사포닌, DEAE-덱스트란, 중성 오일 (예를 들면, 미글리올), 식물성 오일 (예를 들면, 낙화생유), 리포좀, Pluronic 폴리올 또는 Ribi 보조제 시스템 (예를 들면, GB-A-2 189 141 참고)을 포함한다. "Pluronic"은 등록 상표명이다. 면역화되는 환자는 미생물로 인한 감염으로부터 보호될 것이 필요한 환자이다.
본 발명은 또한 본 발명의 폴리펩티드 또는 이의 변이체 또는 단편, 또는 이의 융합체, 또는 본 발명의 폴리뉴클레오티드 또는 이의 변이체 또는 단편, 또는 이의 융합체, 및 전술한 약학적으로 허용가능한 담체를 포함하는 약학 조성물을 포함한다.
본 발명의 전술한 항원 (또는 상기 항원을 코딩하는 폴리뉴클레오티드) 또는 이의 제형물은 경구 및 비경구 (예를 들면, 피하 또는 근육내) 주사를 포함하는 임의의 통상적인 방법에 의해 투여될 수 있다. 상기 치료는 기간에 걸쳐 단일 투여 또는 복수의 투여로 이루어질 수 있다.
이의 항원 성분 (또는 폴리뉴클레오티드)에 의존하는 본 발명의 백신은 인간 의학 및 수의학의 분야에서 유용할 수 있다는 것을 인식할 것이다.
미생물에 의해 야기된 질환은 가축 동물과 같은 많은 동물에서 알려져 있다. 본 발명의 백신은 적당한 항원 또는 상기 항원을 코딩하는 폴리뉴클레오티드를 포함할 때, 인간뿐만 아니라, 예를 들면, 소, 양, 돼지, 말, 개 및 고양dl, 및 병아리, 칠면조, 오리 및 거위와 같은 가금류에 유용하다.
그리하여, 본 발명은 또한 개인에게 전술한 항원 (또는 상기 항원을 코딩하는 폴리뉴클레오티드) 또는 백신을 투여하는 것을 포함하는, 미생물에 대한 개인을 예방접종하는 방법을 포함한다. 본 발명은 또한 개인을 예방접종하기 위한 백신의 제조에서 전술한 항원 (또는 상기 항원을 코딩하는 폴리뉴클레오티드)의 용도를 포함한다.
본 발명의 항원은 백신에서 유일한 항원으로서 이용될 수 있거나 또는 동일 또는 상이한 질병 미생물에 대한 것이든지 간에 기타 항원과 조합되어 이용될 수 있다. 수막구균에 관하여, NmB에 대해 반응성인 수득된 항원은 A 및/또는 C 혈청군에 대한 백신에 이용된 성분과 조합될 수 있다. 이는 또한 해모필루스 (Haemophilus) 및/또는 스트렙토코커스 뉴모니애 (Streptococcus pneumoniae)에 대한 보호를 제공하는 항원 성분과 편리하게 조합될 수 있다. 부가적인 항원 성분은 폴리펩티드일 수 있거나 또는 이는 폴리사카라이드와 같은 기타 항원 성분일 수 있다. 폴리사카라이드는 또한 면역 반응을 증진시키기 위해 이용될 수 있다 (예를 들면, Makela et al (2002) Expert Rev. Vaccines 1, 399-410 참고).
상기 항원이 전술한 (및 실시예에서) 임의의 유전자에 의해 코딩된 폴리펩티드 또는 전술한 변이체 또는 단편 또는 융합체 (또는 상기 항원을 코딩하는 폴리뉴클레오티드)이며, 예방접종되는 질환이 수막구균 감염 (수막구균 질환)이라면 상기 백신 및 예방접종 방법에서 특히 바람직하다.
본 발명은 하기 비제한적인 실시예를 참고하여 더욱 상세히 기재될 것이다.
실시예
1:
수막구균에서
면역원에 대한 유전자 스크리닝 (
GSI
)
본 실시예에서 GSI의 적용이 살균 항체에 의한 사멸에 덜 민감한 균주에 대한 수막구균의 삽입 돌연변이체의 라이브러리를 스크리닝하는 것을 포함한다. GSI는 PCT/GB2005/005441 (2005년 7월 5일에 WO 2005/060995로서 공개됨)에 더욱 상세 히 기재된다.
우리는 동일한 균주의 캡슐 마이너스에 대해 마우스에서 상승된 혈청을 이용하여, 서열결정된 NmB 분리주인 MC58의 돌연변이체의 라이브러리를 스크리닝함으로써 GSI의 유효성을 입증하였다. 총 40,000개의 돌연변이체를 상동성 균주를 이용한 복막내 면역화에 의해 마우스에서 상승된 혈청으로 분석하였으며; 상기 혈청의 SBA는 야생형 균주에 대해 약 2,000이다. 생존하는 돌연변이체는 라이브러리를 1:560 희석으로 혈청에 노출할 때 (이는 모든 야생형 박테리아를 사멸시킴) 검출하였다. 생존하는 돌연변이체에서 트랜스포존 삽입이 사멸에 저항하는 능력에 관련된 것인지를 확립하기 위해, 돌연변이를 모 균주 내로 역교배하고, 상기 역교배된 돌연변이체를 SBA에서 야생형보다 사멸에 더욱 내성이 있는 것으로 확인하였다. 상기 트랜스포존에 의해 영향을 받은 유전자 서열을 마커 구조 (rescue)에 의해 트랜스포존 삽입 자리를 분리함으로써 조사하였다. 우리는 영향받은 유전자 중에서 2개가 TspA 및 NMB0338라는 것을 발견하였다. TspA는 강한 CD4+ T 세포 반응을 유도하는 표면 항원이며, 환자 유래의 혈청에 의해 인식된다 (Kizil et al (1999) Infect Immun. 67, 3533-41). NMB0338는 2개의 막횡단 도메인을 포함하는 것으로 예상되는 폴리펩티드를 코딩하는 이전에 알려지지 않은 기능의 유전자이며, 세포 표면에 위치한다. NMB0338에 의해 코딩되는 아미노산 서열은 하기이다:
MERNGVFGKIVGNRILRMSSEHAAASYPKPCKSFKLAQSWFRVRSCLGGVFIYGANMKLIYTVIKIIILLLFLLLAVINTDAVTFSYLPGQKFDLPLIVYLFGAFWGIIFGMFALFGRLLSLRGENGRLRAEVKKNARLTGKELTAPPAQNAPESTKQP
공중보건 의무와 별개로, GSI에 대해 NmB를 이용하는 몇 가지 실질적인 이점이 있다: a) 박테리아가 유전적으로 다루기 쉬우며; b) 이펙터 (effector) 면역 기작에 의한 박테리아의 사멸은 분석에 직접적이며; c) 게놈 서열은 상이한 혈청군 및 클론 계통의 3가지 분리주 (혈청군 A, B 및 C에 대해 각각 IV-A, ET-5, 및 ET-37)에 대해 유용하며; d) 잘 규명된 임상 자원이 상기 연구에 유용하다.
GSI는 2가지 잠재적인 한계를 가진다. 첫째, 살균 항체의 표적이 필수적일 수 있다. 이는 NmB에서 살균 항체의 모든 공지된 표적은 비필수적이며, 현재로 인증받은 박테리아 백신은 필수적인 유전자 산물을 표적으로 하지 않으므로, 가능하지 않을 것 같다. 둘째, 혈청은 다중 항원에 대한 항체를 포함하며, 단일 항원의 손실은 돌연변이체의 생존에 영향을 주지 않을 것이다. 우리는 이미 상동성 균주에 대해 상승된 혈청을 이용한 선발 동안조차도, 관련 항원은 여전히 적당한 혈청 희석액을 이용하여 동정된다는 것을 보여주었다.
GSI의 주요 장점은 하기이다: 1) 고처리량 단계는 기술적으로 요구되거나 또는 비싼 절차 (예를 들면, 발현/정제 및 면역화)를 포함하지 않으며, 2) 단지 동물 데이타에 의존하는 것보다 인간 시료가 분석에 이용될 수 있다. GSI는 더 작은 수의 후보물질의 더욱 상세한 분석을 허용하면서, 살균 활성을 유도하는 표면 단백질의 서브세트를 신속하게 지적할 것이다.
1. GSI를 이용한 살균 항체의 표적의 동정
이종 균주에 대해 상승된 뮤린 혈청, 및 인간 혈청을 이용하여 교차반응성 항원을 동정한다. 상기 혈청은 하기로부터 수득한다:
i) 이종 균주를 이용한 전신 경로에 의해 면역화된 마우스; 상기 균주는 동일한 면역형 및 서브혈청형을 갖는 분리주를 피하기 위해 선발 및/또는 구축될 것이다.
ii) 수막구균의 공지된 분리주로 감염된 환자 유래의 급성 및 회복기 혈청 (Northwick Park의 Dr R. Wall이 제공함)
iii) NmB 분리주인 H44/76로부터 유도된 지정된 세포 외부 소포 (OMV) 백신을 수용한 지원자 유래의 면역화전 및 면역화 후 시료 (수막구균 기준 실험실이 제공함).
상기 유래의 혈청의 각각은 특이적 장점 및 단점을 가진다.
| 혈청 유래 | 장점 | 단점 |
| 뮤린 | 1) 지정된 항원 노출. 2) 면역반응을 생성하기 위해 유전적으로 변형된 균주의 이용 3) 나이브 시료 유용 4) 개개의 반응 조사 | 1) 물질의 동물 유래 |
| 환자 혈청 | 1) 인간 물질 2) 공지된 균주 노출 3) 급성 및 회복기 혈청 유용 | 1) 배경 면역 2) 제한된 물질 |
| H4476 OMV를 이용한 면역화에 이은 혈청 | 1) 인간 물질 2) 지정된 항원 노출 3) 면역화 전후 혈청 유용 4) 개개의 반응 조사 | 1) 배경 면역 2) 제한된 물질 |
a) 이종 균주 (즉, 서열결정된 혈청군 A 또는 C 균주)로 면역화된 동물 유래의 혈청을 GSI에 이용하여 MC58 돌연변이체의 라이브러리를 선발한다. 우리는 살아있는 약독화된 NmB 를 이용한 면역화가 혈청군 A 및 C 균주에 대해 교차반응성 살균 항체 반응을 유도한다는 것을 보여주었다. 인간 혈청에도 불구하고 증진된 생존을 갖는 돌연변이체가 없는 항원이 파괴된 유전자의 마커 구조에 의해 동정된 다.
b) 이종 혈청에 의한 사멸에 대해 내성을 부여하는 돌연변이가 동정되며, 어느 유전자 산물이 또한 서열결정된 혈청군 A 및 C 균주인 각각 Z2491 및 FAM18의 사멸 표적인지를 결정한다. 상기 게놈 데이타베이스를 상기 유전자의 상동체에 대해 조사한다. 상동체가 존재한다면, 트랜스포존 삽입은 MC58 돌연변이체로부터 증폭되며, 형질전환에 의해 혈청군 A 및 C 균주 내로 도입된다. 각 혈청군의 상기 돌연변이체 및 야생형 균주의 상대적 생존을 비교한다. 그리하여, GSI는 살균 활성의 표적이 혈청군, 면역형 및 서브혈청형과 무관하게, 수막구균의 다양한 균주에서 보존되며, 접근가능한지에 대한 정보를 신속하게 제공할 수 있다.
c) 마우스에서 상승된 혈청에 대한 증진된 생존을 갖는 돌연변이체를 회복기 환자 유래의 인간 혈청 또는 이종 OMV 백신 (H44/76로부터 유래)을 이용하여 시험하였다. 이는 상기 표적이 인간에서 살균 항체를 유도할 수 있는지의 중요한 문제를 제시한다. 기타 백신 접근과 함께, 상기 정보는 백신 후보물질의 GMP 제조를 요하는 임상 시험의 후기, 비싼 단계에서 단지 수득된다.
장점은 GSI가 간단한, 유용한 기술을 이용하여 수행된 고처리량 분석이라는 것이다. 인간에서 살균 항체를 유도하며, 복수 균주의 사멸을 매개하는 항원은 GSI가 이용된 박테리아 균주 및 혈청에 대해 유연성이 있을 때 신속하게 동정될 수 있다. 인간 혈청을 이용하여 선발된 돌연변이체는 뮤린 혈청에 의해 선발된 것과 동일한 방식으로 분석된다.
2. 재조합 GSI 항원의 항체 반응의 평가
회복기 환자 유래의 혈청 및 백신에 의해 인식되는 살균 항체의 표적인 단백질은 시판되는 벡터를 이용하여 대장균에서 발현된다. 해당하는 개방형 해독틀은 MC58로부터 PCR에 의해 증폭되며, pCR Topo CT 또는 pBAD/His와 같은 벡터 내로 연결되어 각각 T7 또는 아라비노스-유도성 프로모터의 제어하에 단백질 발현을 허용한다. 총 세포 단백질로부터 재조합 단백질의 정제는 니켈 또는 코발트 칼럼 상에서 단백질의 C 말단에 융합된 His Tag를 통해 수행된다.
성체 뉴질랜드 백색 토끼를 프로인트 불완전 보조제와 함께 25㎍의 정제된 단백질을 이용한 피하 주사에 의해 4주에 의해 분리된 2가지 경우에 대해 면역화하였다. 동물 유래의 혈청을 전체 세포 ELISA에 의해 기존의 항-Nm 항체에 대한 면역화 전에 검사할 것이다. 1:2 미만의 초기 혈청 역가를 가지는 동물을 면역화 실험에 이용한다. 면역화 후 혈청을 두번째 면역화 후 2주째에 수득한다. 특이적인 항체가 상승되었는지를 확인하기 위해, 면역화 전 및 후 혈청을 i) 정제된 단백질에 대한 웨스턴 분석 및 ii) 야생형 및 해당하는 돌연변이체 (GSI에 의해 생성됨) 유래의 세포를 이용한 ELISA에 의해 시험하였다.
SBA는 토끼 면역 혈청을 이용하여 MC58 (상동성 균주), 및 서열결정된 혈청군 A 및 C 균주에 대해 수행될 것이다. 상기 분석은 적어도 2가지 경우에 3반복으로 수행될 것이다. 8 초과의 SBA는 유의한 것으로 고려될 것이다. 상기 결과는 단백질 후보물질이 재조합 단백질로서 살균 항체를 유도할 수 있는지의 증거를 제공한다.
3. GSI 항원의 보호 효능의 확립
살아있는 박테리아 챌린지에 대해 동물을 보호하는 이의 능력에 대해 모든 후보물질을 시험하였는데, 이는 면역 (세포성 또는 체액성)의 임의의 양태가 단일 분석에서 평가되는 것을 허용하기 때문이다. 우리는 살아있는 박테리아 감염에 대한 활성 면역화 및 보호 모델을 확립하였다. 상기 모델에서, 성체 마우스는 0 및 21일에 면역화되며, 28일에 철 덱스트란 (보충 철 소스로서) 중에서 복막내로 MC58의 106 또는 107 CFU의 살아있는 박테리아 챌린지를 받는다. 상기 모델은 Tbps를 이용한 면역화의 보호 효능의 평가에 대해 기재된 것[Danve et al (1993) Vaccine 11, 1214-1220]과 유사하다. 비면역화된 동물은 감염 4시간 내에 균혈증을 나타내며, 24시간에 전신성 병의 징후를 보여준다. 우리는 이미 살아있는 수막구균 챌린지에 대해 약독화된 Nm 균주 및 단백질 항원 양자의 보호 효능을 입증할 수 있었으며; PorA는 살균 항체를 유도하는 외막 단백질이나, 광대한 항원 변이때문에 주요 백신 후보물질은 아니다 (Bart et al (1999) Infect Immun. 67, 3832- 3846).
6주령 BALB/c 마우스 (그룹 크기, 35마리 동물)는 0 및 21일에 피하로 프로인트 불완전 보조제와 함께 25㎍의 재조합 단백질을 투여받은 후, 28일에 복막내로 MC58의 106 (15마리 동물) 또는 107 (15마리 동물) CFU로 챌린지한다. 2가지 챌린지 투여량을 이용하여 고 및 저 챌린지 투여량에서 백신 효능을 조사하였으며; 혈청을 각 그룹에서 남아있는 5마리 동물, 및 첫번째 면역화 전 5마리 동물로부터 28일에 수득하고, 추가의 면역 분석을 위해 -70℃에 저장한다. 대조군의 동물은 i) 보조제 단독, ii) 재조합 재폴딩된 PorA, 및 iii) 살아있는, 약독화된 Nm 균주를 투여받는다. 대조군에서 동물의 전체 수를 줄이기 위해, 5가지 후보 세트를 한번에 시험할 것이다 (그룹 수 = 5 후보 + 3 대조군). 그룹에서 동물의 생존은 Mann Whitney U Test에 의해 비교된다. 15 마우스/투여의 그룹 크기에 대해, 실험은 그룹 간에 생존에서 25% 차이를 보여주도록 강력하게 하였다.
챌린지에 대해 현저한 보호를 보여주는 백신에 대해, 상기 발견을 확인하기 위해 반복 실험을 수행한다. 더욱이, 후보물질을 이용한 예방접종이 또한 균혈증에 대한 보호를 유도하는지 확립하기 위해, 균혈증 수준은 제2 실험 동안 결정되며; 면역화된 및 비면역화된 동물에서 감염 후 22시간에 (균혈증이 이 시간에 최대임) 혈액을 샘플링한다. 예방접종된 동물에서 균혈증의 현저한 감소가 있는지를 결정하기 위해 결과를 two-tailed Student-T test를 이용하여 분석한다.
이용된 추가의 재료 및 방법
수막구균의 돌연변이유발
수막구균을 이용한 연구를 위해, 돌연변이체를 시험관 내 돌연변이유발에 의해 구축하였다. 수막구균 유래의 게놈 DNA를 카나마이신에 대한 내성을 코딩하는 마커를 포함하는 Tn5 유도체, 및 대장균에서 기능성인 복제 원점과 함께 돌연변이유발하였다. 상기 성분은 복합의 Tn5 말단에 의해 묶였다. 전위 반응을 Tn5의 과활성 변이체를 이용하여 수행하고, DNA는 ATP 및 뉴클레오티드의 존재하에 T4 DNA 중합효소 및 리가아제를 이용하여 복구하였다. 상기 복구된 DNA를 이용하여 수막구균을 형질전환하여 카나마이신 내성이 되게 하였다. 서던 분석으로 각 돌연변이체가 트랜스포존의 단일 삽입을 단지 포함하고 있다는 것을 확인하였다.
혈청 살균 분석 (SBA)
박테리아를 고체 배지 (Levanthals 보충을 갖는 뇌 심장 침출 배지) 상에서 밤새 키운 후, 실험날 아침에 4시간 동안 고체 배지에 재스트리킹하였다. 이 시간 후에, 박테리아를 인산완충염수 내로 수확하고, 갯수를 세었다. SBA를 보체 소스 (어린 토끼 또는 인간), 및 대략 105 집락형성단위를 포함하는 1 ml 부피에서 수행하였다. 상기 박테리아를 인큐베이션 말기에 수집하고, 고체 배지에 도말하여 생존하는 박테리아를 회수하였다.
트랜스포존 삽입 자리의 분리
게놈 DNA는 표준 방법에 의해 목적 돌연변이체로부터 회수되고, 3시간 동안 PvuII, EcoRV, 및 DraI으로 절단된 후, 페놀 추출에 의해 정제될 것이다. 상기 DNA를 이어서 T4 DNA 리가아제의 존재하에 16℃에서 밤새 100㎕ 부피에서 자가 연결하고, 침전시킨 후, 전기천공법에 의해 카나마이신 내성에 대해 대장균을 형질전환할 것이다.
실시예
2: 추가 스크리닝 및 이의 결과
GSI를 이용하여 MC58의 대략 40,000 삽입 돌연변이체의 라이브러리를 스크리닝하였다. 상기 라이브러리를 pACYC184 유래의 복제 원점을 갖는 트랜스포존을 이용하여, 시험관 내 Tn5 돌연변이유발에 의해 구축하였다.
MC58은 수막구균의 혈청군 B 분리주이며, 상기 균주의 완전한 게놈 서열이 알려져 있으므로, 이를 선택하였다.
상기 라이브러리를 항상 대조군으로서 야생형 균주와 함께 스크리닝하고, 상기 라이브러리 및 야생형으로부터 회수된 콜로니 수를 보여준다.
뮤린 혈청을 이용한 선발
초기에 상기 라이브러리를 약독화된 균주 YH102를 이용하여 면역화된 동물 유래의 혈청을 이용하여 분석하였다. 성체 마우스 (Balb/C)는 3가지 경우에 복막내로 108 집락형성단위를 투여받았으며, 혈청을 최종 면역화 후 10일에 수집하였다.
상기 스크린은 혈청 사멸에 대한 증진된 내성을 갖는 수 개의 돌연변이체를 동정하였다: 이는 개개의 돌연변이체를 분리하고, 원래의 유전 배경에서 돌연변이를 재구축하고, 야생형에 대한 매개된 용균을 보충하는 이의 감수성에 대해 개개의 돌연변이체를 재시험함으로써 확인되었다. 상기 트랜스포존 삽입은 하기 유전자에 있다:
폴리펩티드의 분석은 2개의 막횡단 도메인 (잔기 54-70 및 88-107)을 가지는 것을 예상한다는 것을 나타낸다. 그리하여, 영역 1-53, 및 108-말단 (C-말단)의 단편이 면역원으로서 특히 유용할 수 있다.
백신접종자 혈청을 이용한 선발
맨체스터에 있는 Meningococcal Reference Laboratory 유래의 혈청은 우리에게 유용하게 제조되었다. 상기 혈청은 지원자의 OMV 면역화의 임상 시험에서 왔다.
백신 Cl 혈청에 의해 선발된 돌연변이체 (1회 스크리닝함)
하기 서열을 분리하였다.
NMB0338 (상기와 같음)
백신접종자의 17 D 혈청에 의해 선발된 돌연변이체 (단지 1회 스크리닝함)
환자의 혈청을 이용한 선발
우리는 스크리닝을 위해 우리에게 유용한 급성 및 회복기 혈청의 집합을 가진다. 이는 수막구균의 상이한 혈청군으로 감염된 개인 유래이다. 스크리닝을 급성 (A) 또는 회복기 (C) 혈청으로 수행하였다. 혈청의 급성 감염 및 수집 사이의 기간은 2주 내지 3개월이었다.
하기 부가적인 항원을 본질적으로 전술한 방법론을 이용하여 동정하였다:
서열 목록
서열번호 서열
1 NMB0341 DNA
2 NMB0341 단백질
3 NMB1583 DNA
4 NMB1583 단백질
5 NMB1345 DNA
6 NMB1345 단백질
7 NMB0738 DNA
8 NMB0738 단백질
9 NMB0792 DNA
10 NMB0792 단백질
11 NMB0279 DNA
12 NMB0279 단백질
13 NMB2050 DNA
14 NMB2050 단백질
15 NMB1335 DNA
16 NMB1335 단백질
17 NMB2035 DNA
18 NMB2035 단백질
19 NMB1351 DNA
20 NMB1351 단백질
21 NMB1574 DNA
22 NMB1574 단백질
23 NMB1298 DNA
24 NMB1298 단백질
25 NMB1856 DNA
26 NMB1856 단백질
27 NMBOl19 DNA
28 NMBOl19 단백질
29 NMB1705 DNA
30 NMB1705 단백질
31 NMB2065 DNA
32 NMB2065 단백질
33 NMB0339 DNA
34 NMB0339 단백질
35 NMB0401 DNA
36 NMB0401 단백질
37 NMB1467 DNA
38 NMB1467 단백질
39 NMB2056 DNA
40 NMB2056 단백질
41 NMB0808 DNA
42 NMB0808 단백질
43 NMB0774 DNA
44 NMB0774 단백질
45 NMA0078 DNA
46 NMA0078 단백질
47 NMBO337 DNA
48 NMB0337 단백질
49 NMB0191 DNA
50 NMB0191 단백질
51 NMB171O DNA
52 NMB1710 단백질
53 NMB0062 DNA
54 NMB0062 단백질
55 NMB1333 DNA
56 NMB1333 단백질
57 NMB0377 DNA
58 NMB0377 단백질
59 NMB0264 DNA
60 NMB0264 단백질
61 NMB1036 DNA
62 NMB1036 단백질
63 NMB1176 DNA
64 NMB1176 단백질
65 NMB1359 DNA
66 NMB1359 단백질
67 NMBl138 DNA
68 NMB1138 단백질
<110> Imperial College Innovations Limited
<120> Vaccines and their use
<130> ICOBW/P34002PC
<140> PCT/GB2005/005113
<141> 23/12/05
<150> PCT/GB2004/005441
<151> 23/12/04
<160> 68
<170> SeqWin99
<210> 1
<211> 2628
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0341 (TspA) DNA sequence
<400> 1
atgcccgccg gccgactgcc ccgccgatgc ccgatgatga cgaaatttac agactgtacg 60
cggtcaaacc gtattcagcc gccaacccac aggggataca tcttgaaaaa caacagacaa 120
atcaaactga ttgccgcctc cgtcgcagtt gccgcatcct ttcaggcaca tgctggactg 180
ggcggactga atatccagtc caaccttgac gaaccctttt ccggcagcat taccgtaacc 240
ggcgaagaag ccaaagccct gctaggcggc ggcagcgtta ccgtttccga aaaaggcctg 300
accgccaaag tccacaagtt gggcgacaaa gccgtcattg ccgtttcttc cgaacaggca 360
gtccgcgatc ccgtcctggt gttccgcatc ggcgcaggcg cacaggtacg cgaatacacc 420
gccatcctcg atcctgtcgg ctactcgccc aaaaccaaat ctgcactttc agacggcaag 480
acacaccgca aaaccgctcc gacagcagag tcccaagaaa atcaaaacgc caaagccctc 540
cgcaaaaccg ataaaaaaga cagcgcgaac gcagccgtca aaccggcata caacggcaaa 600
acccataccg tccgcaaagg cgaaacggtc aaacagattg ccgccgccat ccgcccgaaa 660
cacctgacgc tcgaacaggt tgccgatgcg ctgctgaagg caaacccaaa tgtttccgca 720
cacggcagac tgcgtgcggg cagcgtgctt cacattccga atctgaacag gatcaaagcg 780
gaacaaccca aaccgcaaac ggcgaaaccc aaagccgaaa ccgcatccat gccgtccgaa 840
ccgtccaaac aggcaacggt agagaaaccg gttgaaaaac ctgaagcaaa agttgccgcg 900
cccgaagcaa aagcggaaaa accggccgtt cgacccgaac ctgtacccgc tgcaaatact 960
gccgcatcgg aaaccgctgc cgaatccgcc ccccaagaag ccgccgcttc tgccatcgac 1020
acgccgaccg acgaaaccgg taacgccgtt tccgaacctg tcgaacaggt ttctgccgaa 1080
gaagaaaccg aaagcggact gtttgacggt ctgttcggcg gttcgtacac cttgctgctt 1140
gccggcggag gcgcggcatt aatcgccctg ctgctgcttt tgcgccttgc ccaatccaaa 1200
cgcgcgcgcc gtaccgaaga atccgtccct gaggaagagc ctgaccttga cgacgcggca 1260
gacgacggca tagaaatcac ctttgccgaa gtcgaaactc cggcaacgcc cgaacccgct 1320
ccgaaaaacg atgtaaacga cacacttgcc ttagatgggg aatctgaaga agagttatcg 1380
gcaaaacaaa cgttcgatgt cgaaaccgat acgccttcca accgcatcga cttggatttc 1440
gacagcctgg cagccgcgca aaacggcatt ttatccggcg cacttacgca ggatgaagaa 1500
acccaaaaac gcgcggatgc cgattggaac gccatcgaat ccacagacag cgtgtacgag 1560
cccgagacct tcaacccgta caaccctgtc gaaatcgtca tcgacacgcc cgaaccggaa 1620
tctgtcgccc aaactgccga aaacaaaccg gaaaccgtcg ataccgattt ctccgacaac 1680
ctgccctcaa acaaccatat cggcacagaa gaaacagctt ccgcaaaacc tgcctcaccc 1740
tccggactgg caggcttcct gaaggcttcc tcgcccgaaa ccatcttgga aaaaacagtt 1800
gccgaagtcc aaacaccgga agagttgcac gatttcctga aagtgtacga aaccgatgcc 1860
gtcgcggaaa ctgcgcctga aacgcccgat ttcaacgccg ccgcagacga tttgtccgca 1920
ttgcttcaac ctgccgaagc accgtccgtt gaggaaaata taacggaaac cgttgccgaa 1980
acacccgact tcaacgccac cgcagacgat ttgtccgcat tacttcaacc ttctaaagta 2040
cctgccgttg aggaaaatgc agcggaaacc gttgccgatg atttgtccgc actgttgcaa 2100
cctgctgaag caccggccgt tgaggaaaat gtaacggaaa ccgttgccga aacacccgat 2160
ttcaacgcca ccgcagacga tttgtccgca ttacttcaac cttctgaagc acctgccgtt 2220
gaggaaaatg cagcggaaac cgttgccgat gatttgtccg cactgttgca acctgctgaa 2280
gcaccggccg ttgaggaaaa tgcagcggaa atcactttgg aaacgcctga ttccaacacc 2340
tctgaggcag acgctttgcc cgacttcctg aaagacggcg aggaggaaac ggtagattgg 2400
agcatctacc tctcggaaga aaatatccca aataatgcag ataccagttt cccttcggaa 2460
tctgtaggtt ctgacgcgcc ttccgaagcg aaatacgacc ttgccgaaat gtatctcgaa 2520
atcggcgacc gcgatgccgc tgccgagaca gtgcagaaat tgctggaaga agcggaaggc 2580
gacgtactca aacgtgccca agcattggcg caggaattgg gtatttga 2628
<210> 2
<211> 875
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0341 (TspA) protein sequence
<400> 2
Met Pro Ala Gly Arg Leu Pro Arg Arg Cys Pro Met Met Thr Lys Phe
1 5 10 15
Thr Asp Cys Thr Arg Ser Asn Arg Ile Gln Pro Pro Thr His Arg Gly
20 25 30
Tyr Ile Leu Lys Asn Asn Arg Gln Ile Lys Leu Ile Ala Ala Ser Val
35 40 45
Ala Val Ala Ala Ser Phe Gln Ala His Ala Gly Leu Gly Gly Leu Asn
50 55 60
Ile Gln Ser Asn Leu Asp Glu Pro Phe Ser Gly Ser Ile Thr Val Thr
65 70 75 80
Gly Glu Glu Ala Lys Ala Leu Leu Gly Gly Gly Ser Val Thr Val Ser
85 90 95
Glu Lys Gly Leu Thr Ala Lys Val His Lys Leu Gly Asp Lys Ala Val
100 105 110
Ile Ala Val Ser Ser Glu Gln Ala Val Arg Asp Pro Val Leu Val Phe
115 120 125
Arg Ile Gly Ala Gly Ala Gln Val Arg Glu Tyr Thr Ala Ile Leu Asp
130 135 140
Pro Val Gly Tyr Ser Pro Lys Thr Lys Ser Ala Leu Ser Asp Gly Lys
145 150 155 160
Thr His Arg Lys Thr Ala Pro Thr Ala Glu Ser Gln Glu Asn Gln Asn
165 170 175
Ala Lys Ala Leu Arg Lys Thr Asp Lys Lys Asp Ser Ala Asn Ala Ala
180 185 190
Val Lys Pro Ala Tyr Asn Gly Lys Thr His Thr Val Arg Lys Gly Glu
195 200 205
Thr Val Lys Gln Ile Ala Ala Ala Ile Arg Pro Lys His Leu Thr Leu
210 215 220
Glu Gln Val Ala Asp Ala Leu Leu Lys Ala Asn Pro Asn Val Ser Ala
225 230 235 240
His Gly Arg Leu Arg Ala Gly Ser Val Leu His Ile Pro Asn Leu Asn
245 250 255
Arg Ile Lys Ala Glu Gln Pro Lys Pro Gln Thr Ala Lys Pro Lys Ala
260 265 270
Glu Thr Ala Ser Met Pro Ser Glu Pro Ser Lys Gln Ala Thr Val Glu
275 280 285
Lys Pro Val Glu Lys Pro Glu Ala Lys Val Ala Ala Pro Glu Ala Lys
290 295 300
Ala Glu Lys Pro Ala Val Arg Pro Glu Pro Val Pro Ala Ala Asn Thr
305 310 315 320
Ala Ala Ser Glu Thr Ala Ala Glu Ser Ala Pro Gln Glu Ala Ala Ala
325 330 335
Ser Ala Ile Asp Thr Pro Thr Asp Glu Thr Gly Asn Ala Val Ser Glu
340 345 350
Pro Val Glu Gln Val Ser Ala Glu Glu Glu Thr Glu Ser Gly Leu Phe
355 360 365
Asp Gly Leu Phe Gly Gly Ser Tyr Thr Leu Leu Leu Ala Gly Gly Gly
370 375 380
Ala Ala Leu Ile Ala Leu Leu Leu Leu Leu Arg Leu Ala Gln Ser Lys
385 390 395 400
Arg Ala Arg Arg Thr Glu Glu Ser Val Pro Glu Glu Glu Pro Asp Leu
405 410 415
Asp Asp Ala Ala Asp Asp Gly Ile Glu Ile Thr Phe Ala Glu Val Glu
420 425 430
Thr Pro Ala Thr Pro Glu Pro Ala Pro Lys Asn Asp Val Asn Asp Thr
435 440 445
Leu Ala Leu Asp Gly Glu Ser Glu Glu Glu Leu Ser Ala Lys Gln Thr
450 455 460
Phe Asp Val Glu Thr Asp Thr Pro Ser Asn Arg Ile Asp Leu Asp Phe
465 470 475 480
Asp Ser Leu Ala Ala Ala Gln Asn Gly Ile Leu Ser Gly Ala Leu Thr
485 490 495
Gln Asp Glu Glu Thr Gln Lys Arg Ala Asp Ala Asp Trp Asn Ala Ile
500 505 510
Glu Ser Thr Asp Ser Val Tyr Glu Pro Glu Thr Phe Asn Pro Tyr Asn
515 520 525
Pro Val Glu Ile Val Ile Asp Thr Pro Glu Pro Glu Ser Val Ala Gln
530 535 540
Thr Ala Glu Asn Lys Pro Glu Thr Val Asp Thr Asp Phe Ser Asp Asn
545 550 555 560
Leu Pro Ser Asn Asn His Ile Gly Thr Glu Glu Thr Ala Ser Ala Lys
565 570 575
Pro Ala Ser Pro Ser Gly Leu Ala Gly Phe Leu Lys Ala Ser Ser Pro
580 585 590
Glu Thr Ile Leu Glu Lys Thr Val Ala Glu Val Gln Thr Pro Glu Glu
595 600 605
Leu His Asp Phe Leu Lys Val Tyr Glu Thr Asp Ala Val Ala Glu Thr
610 615 620
Ala Pro Glu Thr Pro Asp Phe Asn Ala Ala Ala Asp Asp Leu Ser Ala
625 630 635 640
Leu Leu Gln Pro Ala Glu Ala Pro Ser Val Glu Glu Asn Ile Thr Glu
645 650 655
Thr Val Ala Glu Thr Pro Asp Phe Asn Ala Thr Ala Asp Asp Leu Ser
660 665 670
Ala Leu Leu Gln Pro Ser Lys Val Pro Ala Val Glu Glu Asn Ala Ala
675 680 685
Glu Thr Val Ala Asp Asp Leu Ser Ala Leu Leu Gln Pro Ala Glu Ala
690 695 700
Pro Ala Val Glu Glu Asn Val Thr Glu Thr Val Ala Glu Thr Pro Asp
705 710 715 720
Phe Asn Ala Thr Ala Asp Asp Leu Ser Ala Leu Leu Gln Pro Ser Glu
725 730 735
Ala Pro Ala Val Glu Glu Asn Ala Ala Glu Thr Val Ala Asp Asp Leu
740 745 750
Ser Ala Leu Leu Gln Pro Ala Glu Ala Pro Ala Val Glu Glu Asn Ala
755 760 765
Ala Glu Ile Thr Leu Glu Thr Pro Asp Ser Asn Thr Ser Glu Ala Asp
770 775 780
Ala Leu Pro Asp Phe Leu Lys Asp Gly Glu Glu Glu Thr Val Asp Trp
785 790 795 800
Ser Ile Tyr Leu Ser Glu Glu Asn Ile Pro Asn Asn Ala Asp Thr Ser
805 810 815
Phe Pro Ser Glu Ser Val Gly Ser Asp Ala Pro Ser Glu Ala Lys Tyr
820 825 830
Asp Leu Ala Glu Met Tyr Leu Glu Ile Gly Asp Arg Asp Ala Ala Ala
835 840 845
Glu Thr Val Gln Lys Leu Leu Glu Glu Ala Glu Gly Asp Val Leu Lys
850 855 860
Arg Ala Gln Ala Leu Ala Gln Glu Leu Gly Ile
865 870 875
<210> 3
<211> 918
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1583 DNA sequence
<400> 3
atgaatttga ctaaaacaca acgccaactg cacaactttc tgaccctcgc ccaagaagca 60
ggttcgctgt ccaagctcgc caaactctgc ggctaccgta cccccgtcgc actctacaaa 120
ctcaaacaac gccttgaaaa gcaggcagaa gacccagatg cacgcggcat ccgtcccagc 180
ctgatggcaa aactcgaaaa acacaccggc aaacccaaag gctggctcga cagaaaacac 240
cgcgaacgca ctgtccccga aaccgccgca gaaagcaccg gaactgccga aacccaaatt 300
gccgaaaccg catctgctgc cggctgccgc agcgttaccg tcaaccgcaa tacctgcgaa 360
acccaaatca ccgtctccat caacctcgac ggcagcggca aaagcaggct ggataccggc 420
gtacccttcc tcgaacacat gatcgatcaa atcgcccgcc acggcatgat tgacatcgac 480
atcagctgca aaggcgacct gcacatcgac gaccaccaca ccgccgaaga catcggcatc 540
acactcggac aagcaatccg gcaggcactc ggcgacaaaa aaggcatccg ccgttacgga 600
cattcctacg tcccgctcga cgaagccctc agccgcgtcg tcatcgacct ttccggccgc 660
cccggactcg tgtacaacat cgaatttacc cgcgcactaa tcggacgttt cgatgtcgat 720
ttgtttgaag aatttttcca cggcatcgtc aaccacagta tgatgaccct gcacatcgac 780
aacctcagcg gcaaaaacgc ccaccatcag gcggaaaccg tattcaaagc cttcgggcgc 840
gccctgcgta tggcagtcga acacgacccg cgcatggcag gacagacccc ctcgaccaaa 900
ggcacgctga ccgcataa 918
<210> 4
<211> 305
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1583 protein sequence
<400> 4
Met Asn Leu Thr Lys Thr Gln Arg Gln Leu His Asn Phe Leu Thr Leu
1 5 10 15
Ala Gln Glu Ala Gly Ser Leu Ser Lys Leu Ala Lys Leu Cys Gly Tyr
20 25 30
Arg Thr Pro Val Ala Leu Tyr Lys Leu Lys Gln Arg Leu Glu Lys Gln
35 40 45
Ala Glu Asp Pro Asp Ala Arg Gly Ile Arg Pro Ser Leu Met Ala Lys
50 55 60
Leu Glu Lys His Thr Gly Lys Pro Lys Gly Trp Leu Asp Arg Lys His
65 70 75 80
Arg Glu Arg Thr Val Pro Glu Thr Ala Ala Glu Ser Thr Gly Thr Ala
85 90 95
Glu Thr Gln Ile Ala Glu Thr Ala Ser Ala Ala Gly Cys Arg Ser Val
100 105 110
Thr Val Asn Arg Asn Thr Cys Glu Thr Gln Ile Thr Val Ser Ile Asn
115 120 125
Leu Asp Gly Ser Gly Lys Ser Arg Leu Asp Thr Gly Val Pro Phe Leu
130 135 140
Glu His Met Ile Asp Gln Ile Ala Arg His Gly Met Ile Asp Ile Asp
145 150 155 160
Ile Ser Cys Lys Gly Asp Leu His Ile Asp Asp His His Thr Ala Glu
165 170 175
Asp Ile Gly Ile Thr Leu Gly Gln Ala Ile Arg Gln Ala Leu Gly Asp
180 185 190
Lys Lys Gly Ile Arg Arg Tyr Gly His Ser Tyr Val Pro Leu Asp Glu
195 200 205
Ala Leu Ser Arg Val Val Ile Asp Leu Ser Gly Arg Pro Gly Leu Val
210 215 220
Tyr Asn Ile Glu Phe Thr Arg Ala Leu Ile Gly Arg Phe Asp Val Asp
225 230 235 240
Leu Phe Glu Glu Phe Phe His Gly Ile Val Asn His Ser Met Met Thr
245 250 255
Leu His Ile Asp Asn Leu Ser Gly Lys Asn Ala His His Gln Ala Glu
260 265 270
Thr Val Phe Lys Ala Phe Gly Arg Ala Leu Arg Met Ala Val Glu His
275 280 285
Asp Pro Arg Met Ala Gly Gln Thr Pro Ser Thr Lys Gly Thr Leu Thr
290 295 300
Ala
305
<210> 5
<211> 1551
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1345 DNA sequence
<400> 5
atgaaaaaac ctttgatttc ggttgcggca gcattgctcg gcgttgcttt gggcacgcct 60
tattatttgg gtgtcaaagc cgaagaaagc ttgacgcagc agcaaaaaat attgcaggaa 120
acgggcttct tgaccgtcga atcgcaccaa tatgagcgcg gctggtttac ctctatggaa 180
acgacggtca tccgtctgaa acccgagttg ctgaataatg cccgaaaata cctgccggat 240
aacctgaaaa cagtgttgga acagccggtt acgctggtta accatatcac gcacggccct 300
ttcgccggcg gattcggcac gcaggcgtac attgaaaccg agttcaaata cgcgcctgaa 360
acggaaaaag ttctggaacg cttttttgga aaacaagtcc cggcttccct tgccaatacc 420
gtttatttta acggcagcgg taaaatggaa gtcagtgttc ccgccttcga ttatgaagag 480
ctgtcgggca tcaggctgca ctgggaaggc ctgacgggag aaacggttta tcaaaaaggt 540
ttcaaaagct accggaacgg ctatgatgcc cccttgttta aaatcaagct ggcagacaaa 600
ggcgatgccg cgtttgaaaa agtgcatttc gattcggaaa cttcagacgg catcaatccg 660
cttgctttgg gcagcagcaa tctgaccttg gaaaaattct ccctagaatg gaaagagggt 720
gtcgattaca acgtcaagtt aaacgaactg gtcaatcttg ttaccgattt gcagattggc 780
gcgtttatca atcccaacgg cagcatcgca ccttccaaaa tcgaagtcgg caaactggct 840
ttttcaacca agaccgggga atcaggcgcg tttatcaaca gtgaagggca gttccgtttc 900
gatacactgg tgtacggcga tgaaaaatac ggcccgctgg acatccatat cgctgccgaa 960
cacctcgatg cttctgcctt aaccgtattg aaacgcaagt ttgcacaaat ttccgccaaa 1020
aaaatgaccg aggaacaaat ccgcaatgat ttgattgccg ccgtcaaagg agaggcttcc 1080
ggactgttca ccaacaatcc cgtattggac attaaaactt tccgattcac gctgccatcg 1140
ggaaaaatcg atgtgggcgg aaaaatcatg tttaaagaca tgaagaagga agatttgaat 1200
caattgggtt tgatgctgaa gaaaaccgaa gccgacatca gaatgagtat tccccaaaaa 1260
atgctggaag acttggcggt cagtcaagca ggcaatattt tcagcgtcaa tgccgaagat 1320
gaggcggaag gcagggcaag tcttgacgac atcaacgaga ccttgcgcct gatggtggac 1380
agtacggttc agagtatggc aagggaaaaa tatctgactt tgaacggcga ccagattgat 1440
actgccattt ctctgaaaaa caatcagttg aaattgaacg gtaaaacgtt gcaaaacgaa 1500
ccggagccgg attttgatga aggcggtatg gtttcagagc cgcagcagta a 1551
<210> 6
<211> 516
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1345 protein sequence
<400> 6
Met Lys Lys Pro Leu Ile Ser Val Ala Ala Ala Leu Leu Gly Val Ala
1 5 10 15
Leu Gly Thr Pro Tyr Tyr Leu Gly Val Lys Ala Glu Glu Ser Leu Thr
20 25 30
Gln Gln Gln Lys Ile Leu Gln Glu Thr Gly Phe Leu Thr Val Glu Ser
35 40 45
His Gln Tyr Glu Arg Gly Trp Phe Thr Ser Met Glu Thr Thr Val Ile
50 55 60
Arg Leu Lys Pro Glu Leu Leu Asn Asn Ala Arg Lys Tyr Leu Pro Asp
65 70 75 80
Asn Leu Lys Thr Val Leu Glu Gln Pro Val Thr Leu Val Asn His Ile
85 90 95
Thr His Gly Pro Phe Ala Gly Gly Phe Gly Thr Gln Ala Tyr Ile Glu
100 105 110
Thr Glu Phe Lys Tyr Ala Pro Glu Thr Glu Lys Val Leu Glu Arg Phe
115 120 125
Phe Gly Lys Gln Val Pro Ala Ser Leu Ala Asn Thr Val Tyr Phe Asn
130 135 140
Gly Ser Gly Lys Met Glu Val Ser Val Pro Ala Phe Asp Tyr Glu Glu
145 150 155 160
Leu Ser Gly Ile Arg Leu His Trp Glu Gly Leu Thr Gly Glu Thr Val
165 170 175
Tyr Gln Lys Gly Phe Lys Ser Tyr Arg Asn Gly Tyr Asp Ala Pro Leu
180 185 190
Phe Lys Ile Lys Leu Ala Asp Lys Gly Asp Ala Ala Phe Glu Lys Val
195 200 205
His Phe Asp Ser Glu Thr Ser Asp Gly Ile Asn Pro Leu Ala Leu Gly
210 215 220
Ser Ser Asn Leu Thr Leu Glu Lys Phe Ser Leu Glu Trp Lys Glu Gly
225 230 235 240
Val Asp Tyr Asn Val Lys Leu Asn Glu Leu Val Asn Leu Val Thr Asp
245 250 255
Leu Gln Ile Gly Ala Phe Ile Asn Pro Asn Gly Ser Ile Ala Pro Ser
260 265 270
Lys Ile Glu Val Gly Lys Leu Ala Phe Ser Thr Lys Thr Gly Glu Ser
275 280 285
Gly Ala Phe Ile Asn Ser Glu Gly Gln Phe Arg Phe Asp Thr Leu Val
290 295 300
Tyr Gly Asp Glu Lys Tyr Gly Pro Leu Asp Ile His Ile Ala Ala Glu
305 310 315 320
His Leu Asp Ala Ser Ala Leu Thr Val Leu Lys Arg Lys Phe Ala Gln
325 330 335
Ile Ser Ala Lys Lys Met Thr Glu Glu Gln Ile Arg Asn Asp Leu Ile
340 345 350
Ala Ala Val Lys Gly Glu Ala Ser Gly Leu Phe Thr Asn Asn Pro Val
355 360 365
Leu Asp Ile Lys Thr Phe Arg Phe Thr Leu Pro Ser Gly Lys Ile Asp
370 375 380
Val Gly Gly Lys Ile Met Phe Lys Asp Met Lys Lys Glu Asp Leu Asn
385 390 395 400
Gln Leu Gly Leu Met Leu Lys Lys Thr Glu Ala Asp Ile Arg Met Ser
405 410 415
Ile Pro Gln Lys Met Leu Glu Asp Leu Ala Val Ser Gln Ala Gly Asn
420 425 430
Ile Phe Ser Val Asn Ala Glu Asp Glu Ala Glu Gly Arg Ala Ser Leu
435 440 445
Asp Asp Ile Asn Glu Thr Leu Arg Leu Met Val Asp Ser Thr Val Gln
450 455 460
Ser Met Ala Arg Glu Lys Tyr Leu Thr Leu Asn Gly Asp Gln Ile Asp
465 470 475 480
Thr Ala Ile Ser Leu Lys Asn Asn Gln Leu Lys Leu Asn Gly Lys Thr
485 490 495
Leu Gln Asn Glu Pro Glu Pro Asp Phe Asp Glu Gly Gly Met Val Ser
500 505 510
Glu Pro Gln Gln
515
<210> 7
<211> 855
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0738 DNA sequence
<400> 7
atgaagatcg tcctgattag cggcctgtcc ggttcgggca agtccgtcgc actgcgccaa 60
atggaagatt cgggttattt ctgcgtggac aatttgcctt tggaaatgtt gcccgcgctg 120
gtgtcgtatc atatcgaacg tgcggacgaa accgaattgg cggtcagcgt cgatgtgcgt 180
tccggcattg acatcggaca ggcgcgggaa cagattgcct ctctgcgcag actggggcac 240
agggttgaag ttttgtttgt cgaggcggaa gaaagcgtgt tggtccgccg gttttccgaa 300
accaggcgag gacatcctct gagcaatcag gatatgacct tgttggaaag cttaaagaaa 360
gaacgggaat ggctgttccc gcttaaagaa atcgcctatt gtatcgacac ttccaagatg 420
aatgcccaac agctccgcca tgcagtccgg cagtggctga aggtcgaacg taccgggctg 480
ctggtgattt tggagtcctt cgggttcaaa tacggtgtgc cgaacaacgc ggattttatg 540
ttcgatatgc gcagcctgcc caacccgtat tacgatcccg agttgaggcc ttacaccggt 600
atggacaagc ccgtttggga ttatttggac ggacagccgc ttgtgcagga aatggttgac 660
gacatcgaaa ggtttgttac gcattggtta ccgcgtttgg aggatgaaag caggagctac 720
gttaccgtcg ccatcggttg cacgggagga cagcaccgtt cggtctatat tgtcgaaaaa 780
ctcgcccgaa ggttgaaagg gcgttatgaa ttgctgatac ggcacagaca ggcgcaaaac 840
ctgtcagacc gctaa 855
<210> 8
<211> 284
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0738 protein sequence
<400> 8
Met Lys Ile Val Leu Ile Ser Gly Leu Ser Gly Ser Gly Lys Ser Val
1 5 10 15
Ala Leu Arg Gln Met Glu Asp Ser Gly Tyr Phe Cys Val Asp Asn Leu
20 25 30
Pro Leu Glu Met Leu Pro Ala Leu Val Ser Tyr His Ile Glu Arg Ala
35 40 45
Asp Glu Thr Glu Leu Ala Val Ser Val Asp Val Arg Ser Gly Ile Asp
50 55 60
Ile Gly Gln Ala Arg Glu Gln Ile Ala Ser Leu Arg Arg Leu Gly His
65 70 75 80
Arg Val Glu Val Leu Phe Val Glu Ala Glu Glu Ser Val Leu Val Arg
85 90 95
Arg Phe Ser Glu Thr Arg Arg Gly His Pro Leu Ser Asn Gln Asp Met
100 105 110
Thr Leu Leu Glu Ser Leu Lys Lys Glu Arg Glu Trp Leu Phe Pro Leu
115 120 125
Lys Glu Ile Ala Tyr Cys Ile Asp Thr Ser Lys Met Asn Ala Gln Gln
130 135 140
Leu Arg His Ala Val Arg Gln Trp Leu Lys Val Glu Arg Thr Gly Leu
145 150 155 160
Leu Val Ile Leu Glu Ser Phe Gly Phe Lys Tyr Gly Val Pro Asn Asn
165 170 175
Ala Asp Phe Met Phe Asp Met Arg Ser Leu Pro Asn Pro Tyr Tyr Asp
180 185 190
Pro Glu Leu Arg Pro Tyr Thr Gly Met Asp Lys Pro Val Trp Asp Tyr
195 200 205
Leu Asp Gly Gln Pro Leu Val Gln Glu Met Val Asp Asp Ile Glu Arg
210 215 220
Phe Val Thr His Trp Leu Pro Arg Leu Glu Asp Glu Ser Arg Ser Tyr
225 230 235 240
Val Thr Val Ala Ile Gly Cys Thr Gly Gly Gln His Arg Ser Val Tyr
245 250 255
Ile Val Glu Lys Leu Ala Arg Arg Leu Lys Gly Arg Tyr Glu Leu Leu
260 265 270
Ile Arg His Arg Gln Ala Gln Asn Leu Ser Asp Arg
275 280
<210> 9
<211> 1416
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0792 DNA sequence
<400> 9
atgaacctgc atgcaaagga caaaacccag catcccgaaa acgtcgagct gctcagtgcg 60
cagaagccga ttaccgactt taagggcctg ctgaccacca ttatttccgc cgtcgtctgt 120
ttcggcattt accacatcct gccttacagc cccgatgcca ataaaggtat cgcgctgctg 180
attttcgttg ccgcactttg gtttaccgag gccgtccaca ttaccgtaac cgcactgatg 240
gtgccgattc tcgccgtcgt actcggtttc cccgacatgg acatcaaaaa ggcgatggct 300
gatttttcca acccgattat ctacattttt ttcggcggct tcgcgcttgc caccgccctg 360
catatgcagc ggctggaccg taaaatcgcc gtcagcctgt tgcgcctgtc gcgcggcaat 420
atgaaagtgg cggttttgat gttgttcctc gttaccgcct ttctgtccat gtggatcagc 480
aacaccgcca ccgccgcgat gatgctgcct ctagcaatgg gtatgctgag ccacctcgac 540
caggaaaaag aacacaaaac ctacgtcttc ctcctgctcg gcatcgccta ttgcgccagc 600
atcggcggct tgggcacgct cgtcggctcg ccgcccaacc tgattgccgc caaagcccta 660
aatctggact tcgtcggctg gatgaagctc ggcctgccga tgatgctgtt gattctgccc 720
ttgatgctgc tctccctgta cgtcatcctc aaacctaatt tgaacgaacg cgtggaaatc 780
aaagccgaat ccatcccttg gacgctgcac cgcgtgatcg cgctgttgat tttccttgcc 840
acagccgccg cgtggatatt cagctccaaa atcaaaaccg ccttcggcat ttccaatccc 900
gacaccgtta tcgccctgag tgccgccgtc gccgtcgtcg tcttcggcgt ggcgcaatgg 960
aaggaagtcg cccgcaatac cgactggggc gtgttgatgc tcttcggcgg cggcatcagc 1020
ctgagcacgc tgttgaaaac atccggcgcg tccgaagcct tgggacagca ggttgccgcc 1080
accttttccg gcgcgcccgc atttttggtg atactcatcg tcgccgcctt cattattttt 1140
ctgaccgagt tcaccagcaa caccgcctcc gccgcattgc ttgtaccgat tttctccggc 1200
atcgctatgc agatggggct gcccgaacaa gtcttggtat tcgtcatcgg catcggcgca 1260
tcttgtgcct tcatgctgcc ggttgccaca ccgcctaacg cgattgtgtt cggcacgggc 1320
ttaatcaagc aacgcgaaat gatgaatgtc ggcatactgc tgaacatcct ctgcgtagta 1380
ttggttgctc tgtgggctta tgctgtactg atgtaa 1416
<210> 10
<211> 471
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0792 protein sequence
<400> 10
Met Asn Leu His Ala Lys Asp Lys Thr Gln His Pro Glu Asn Val Glu
1 5 10 15
Leu Leu Ser Ala Gln Lys Pro Ile Thr Asp Phe Lys Gly Leu Leu Thr
20 25 30
Thr Ile Ile Ser Ala Val Val Cys Phe Gly Ile Tyr His Ile Leu Pro
35 40 45
Tyr Ser Pro Asp Ala Asn Lys Gly Ile Ala Leu Leu Ile Phe Val Ala
50 55 60
Ala Leu Trp Phe Thr Glu Ala Val His Ile Thr Val Thr Ala Leu Met
65 70 75 80
Val Pro Ile Leu Ala Val Val Leu Gly Phe Pro Asp Met Asp Ile Lys
85 90 95
Lys Ala Met Ala Asp Phe Ser Asn Pro Ile Ile Tyr Ile Phe Phe Gly
100 105 110
Gly Phe Ala Leu Ala Thr Ala Leu His Met Gln Arg Leu Asp Arg Lys
115 120 125
Ile Ala Val Ser Leu Leu Arg Leu Ser Arg Gly Asn Met Lys Val Ala
130 135 140
Val Leu Met Leu Phe Leu Val Thr Ala Phe Leu Ser Met Trp Ile Ser
145 150 155 160
Asn Thr Ala Thr Ala Ala Met Met Leu Pro Leu Ala Met Gly Met Leu
165 170 175
Ser His Leu Asp Gln Glu Lys Glu His Lys Thr Tyr Val Phe Leu Leu
180 185 190
Leu Gly Ile Ala Tyr Cys Ala Ser Ile Gly Gly Leu Gly Thr Leu Val
195 200 205
Gly Ser Pro Pro Asn Leu Ile Ala Ala Lys Ala Leu Asn Leu Asp Phe
210 215 220
Val Gly Trp Met Lys Leu Gly Leu Pro Met Met Leu Leu Ile Leu Pro
225 230 235 240
Leu Met Leu Leu Ser Leu Tyr Val Ile Leu Lys Pro Asn Leu Asn Glu
245 250 255
Arg Val Glu Ile Lys Ala Glu Ser Ile Pro Trp Thr Leu His Arg Val
260 265 270
Ile Ala Leu Leu Ile Phe Leu Ala Thr Ala Ala Ala Trp Ile Phe Ser
275 280 285
Ser Lys Ile Lys Thr Ala Phe Gly Ile Ser Asn Pro Asp Thr Val Ile
290 295 300
Ala Leu Ser Ala Ala Val Ala Val Val Val Phe Gly Val Ala Gln Trp
305 310 315 320
Lys Glu Val Ala Arg Asn Thr Asp Trp Gly Val Leu Met Leu Phe Gly
325 330 335
Gly Gly Ile Ser Leu Ser Thr Leu Leu Lys Thr Ser Gly Ala Ser Glu
340 345 350
Ala Leu Gly Gln Gln Val Ala Ala Thr Phe Ser Gly Ala Pro Ala Phe
355 360 365
Leu Val Ile Leu Ile Val Ala Ala Phe Ile Ile Phe Leu Thr Glu Phe
370 375 380
Thr Ser Asn Thr Ala Ser Ala Ala Leu Leu Val Pro Ile Phe Ser Gly
385 390 395 400
Ile Ala Met Gln Met Gly Leu Pro Glu Gln Val Leu Val Phe Val Ile
405 410 415
Gly Ile Gly Ala Ser Cys Ala Phe Met Leu Pro Val Ala Thr Pro Pro
420 425 430
Asn Ala Ile Val Phe Gly Thr Gly Leu Ile Lys Gln Arg Glu Met Met
435 440 445
Asn Val Gly Ile Leu Leu Asn Ile Leu Cys Val Val Leu Val Ala Leu
450 455 460
Trp Ala Tyr Ala Val Leu Met
465 470
<210> 11
<211> 1005
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0279 DNA sequence
<400> 11
atgcaacgac aaatcaaact gaaaaattgg cttcagaccg tttatcccga acgggacttc 60
gatctgactt ttgcggcggc ggatgctgat ttccgccgct atttccgtgc aacgttttca 120
gacggcagca gtgtcgtctg catggatgca ccgcccgaca agatgagtgt cgcaccttat 180
ttgaaagtgc agaaactgtt tgacatggtc aatgtgccgc aggtattgca cgcggacacg 240
gatctggggt ttgtggtatt gaacgacttg ggcaatacga cgtttttgac cgcaatgctt 300
caggaacagg gcgaaacggc gcacaaagcc ctgcttttgg aggcaatcgg cgagttggtc 360
gaattgcaga aggcgagccg tgaaggggtt ttgcccgaat atgaccgtga aacgatgttg 420
cgcgaaatca acctgttccc ggaatggttt gtcgcaaaag aattggggcg cgaattaaca 480
ttcaaacaac gccaactttg gcagcaaacc gtcgatacgc tgctgccgcc cctgttggcg 540
cagcccaaag tctatgtgca ccgcgacttt atcgtccgca acctgatgct gacgcgcggc 600
aggccgggcg ttttagactt ccaagacgcg ctttacggcc cgatttccta cgatttggtg 660
tcgctgttgc gcgatgcctt tatcgaatgg gaagaagaat ttgtcttgga cttggttatc 720
cgctactggg aaaaggcgcg ggctgccggc ttgcccgtcc ccgaagcgtt tgacgagttt 780
taccgctggt tcgaatggat gggcgtgcag cggcacttga aggttgcagg catcttcgca 840
cgcctgtact accgcgacgg caaagacaaa taccgtccgg aaatcccgcg tttcttaaac 900
tatctgcgcc gcgtatcgcg ccgttatgcc gaactcgccc cgctctacgc gctcttggtc 960
gaactggtcg gcgatgaaga actggaaacg ggctttacgt tttaa 1005
<210> 12
<211> 334
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0279 protein sequence
<400> 12
Met Gln Arg Gln Ile Lys Leu Lys Asn Trp Leu Gln Thr Val Tyr Pro
1 5 10 15
Glu Arg Asp Phe Asp Leu Thr Phe Ala Ala Ala Asp Ala Asp Phe Arg
20 25 30
Arg Tyr Phe Arg Ala Thr Phe Ser Asp Gly Ser Ser Val Val Cys Met
35 40 45
Asp Ala Pro Pro Asp Lys Met Ser Val Ala Pro Tyr Leu Lys Val Gln
50 55 60
Lys Leu Phe Asp Met Val Asn Val Pro Gln Val Leu His Ala Asp Thr
65 70 75 80
Asp Leu Gly Phe Val Val Leu Asn Asp Leu Gly Asn Thr Thr Phe Leu
85 90 95
Thr Ala Met Leu Gln Glu Gln Gly Glu Thr Ala His Lys Ala Leu Leu
100 105 110
Leu Glu Ala Ile Gly Glu Leu Val Glu Leu Gln Lys Ala Ser Arg Glu
115 120 125
Gly Val Leu Pro Glu Tyr Asp Arg Glu Thr Met Leu Arg Glu Ile Asn
130 135 140
Leu Phe Pro Glu Trp Phe Val Ala Lys Glu Leu Gly Arg Glu Leu Thr
145 150 155 160
Phe Lys Gln Arg Gln Leu Trp Gln Gln Thr Val Asp Thr Leu Leu Pro
165 170 175
Pro Leu Leu Ala Gln Pro Lys Val Tyr Val His Arg Asp Phe Ile Val
180 185 190
Arg Asn Leu Met Leu Thr Arg Gly Arg Pro Gly Val Leu Asp Phe Gln
195 200 205
Asp Ala Leu Tyr Gly Pro Ile Ser Tyr Asp Leu Val Ser Leu Leu Arg
210 215 220
Asp Ala Phe Ile Glu Trp Glu Glu Glu Phe Val Leu Asp Leu Val Ile
225 230 235 240
Arg Tyr Trp Glu Lys Ala Arg Ala Ala Gly Leu Pro Val Pro Glu Ala
245 250 255
Phe Asp Glu Phe Tyr Arg Trp Phe Glu Trp Met Gly Val Gln Arg His
260 265 270
Leu Lys Val Ala Gly Ile Phe Ala Arg Leu Tyr Tyr Arg Asp Gly Lys
275 280 285
Asp Lys Tyr Arg Pro Glu Ile Pro Arg Phe Leu Asn Tyr Leu Arg Arg
290 295 300
Val Ser Arg Arg Tyr Ala Glu Leu Ala Pro Leu Tyr Ala Leu Leu Val
305 310 315 320
Glu Leu Val Gly Asp Glu Glu Leu Glu Thr Gly Phe Thr Phe
325 330
<210> 13
<211> 1785
<212> DNA
<213> Neisseria meningitidis serogroup B NMB2050 DNA sequence
<400> 13
atggaactga tgactgtttt gctgcctttg gcggcgttgg tgtcgggcgt gttgtttaca 60
tggttgctga tgaagggccg gtttcagggc gagtttgccg gtttgaacgc gcacctggcg 120
gaaaaggcgg caagatgtga ttttgtcgaa caggcacacg gcaaaaccgt gtcggaattg 180
gcggtgttgg acgggaaata ccggcatttg caggacgaaa attatgcttt gggcaaccgt 240
ttttccgcag ccgaaaagca gattgcccat ttgcaggaaa aagaggcgga gtcggcgcgg 300
ctgaagcagt cgtatatcga gttgcaggaa aaggcacagg gtttggcggt tgaaaacgaa 360
cgtttggcaa cgcagctcgg acaggaacgg aaggcgtttg ccgaccaata tgccttggaa 420
cgccaaatcc gccaaagaat cgaaaccgat ttggaagaaa gccgccaaac tgtccgcgac 480
gtgcaaaacg acctttccga tgtcggcaac cgttttgccg cagccgaaaa acagattgcc 540
catttgcagg aaaaagaggc ggaagcggag cggttgaggc agtcgcatac cgagttgcag 600
gaaaaggcac agggtttggc ggttgaaaac gaacgtttgg caacgcaaat cgaacaggaa 660
cgccttgctt ctgaagagaa gctgtccttg ctgggcgagg cgcgcaaaag tttgagcgat 720
cagtttcaaa atcttgccaa cacgattttg gaagaaaaaa gccgccgttt taccgagcag 780
aaccgcgagc agctccatca ggttttgaac ccgctaaacg aacgcatcca cggtttcggc 840
gagttggtca agcaaaccta tgataaagaa tcgcgcgagc ggctgacgtt ggaaaacgaa 900
ttgaaacggc ttcaggggtt gaacgcgcag ctgcacagcg aggcaaaggc cctgaccaac 960
gcgctgaccg gtacgcagaa taaggttcag ggcaattggg gcgagatgat tctggaaacg 1020
gttttggaaa attccggcct tcagaaaggg cgggaatatg tggttcaggc ggcatccgtc 1080
cgaaaagagg aagacggcgg cacgcgccgc ctccagcccg acgttttggt caacctgccc 1140
gacaacaagc agattgtgat tgattccaag gtctcgctga cagcttatgt gcgctacacg 1200
caggcggcgg atgcggatac ggcggcacgc gaactggcgg cacacgttgc cagcatccgt 1260
gcacacatga aaggcttgtc gctgaaggat tacaccgatt tggaaggtgt gaacacattg 1320
gatttcgtct ttatgtttat ccctgtcgaa ccggcctacc tgttggcgtt gcagaatgac 1380
gcgggcttgt tccaagagtg tttcgacaaa cggattatgc tggtcggccc cagtacgctg 1440
ctggcgactt tgaggacggt ggcgaatatt tggcgcaacg aacagcaaaa tcagaacgca 1500
ctggcgattg cggacgaagg cggcaagctg tacgacaagt ttgtcggctt cgtacagacg 1560
ctcgaaagcg tcggcaaagg catcgatcag gcgcaaagca gttttcagac ggcattcaag 1620
caacttgccg aagggcgcgg gaatctggtc ggacgcgccg agaaactgcg tctgttgggc 1680
gtgaaggcag gcaaacaact tcaacgggat ttggtcgagc gttccaatga aacaacggcg 1740
ttgtcggaat ctttggaata cgcggcagaa gatgaagcag tctga 1785
<210> 14
<211> 594
<212> PRT
<213> Neisseria meningitidis serogroup B NMB2050 protein sequence
<400> 14
Met Glu Leu Met Thr Val Leu Leu Pro Leu Ala Ala Leu Val Ser Gly
1 5 10 15
Val Leu Phe Thr Trp Leu Leu Met Lys Gly Arg Phe Gln Gly Glu Phe
20 25 30
Ala Gly Leu Asn Ala His Leu Ala Glu Lys Ala Ala Arg Cys Asp Phe
35 40 45
Val Glu Gln Ala His Gly Lys Thr Val Ser Glu Leu Ala Val Leu Asp
50 55 60
Gly Lys Tyr Arg His Leu Gln Asp Glu Asn Tyr Ala Leu Gly Asn Arg
65 70 75 80
Phe Ser Ala Ala Glu Lys Gln Ile Ala His Leu Gln Glu Lys Glu Ala
85 90 95
Glu Ser Ala Arg Leu Lys Gln Ser Tyr Ile Glu Leu Gln Glu Lys Ala
100 105 110
Gln Gly Leu Ala Val Glu Asn Glu Arg Leu Ala Thr Gln Leu Gly Gln
115 120 125
Glu Arg Lys Ala Phe Ala Asp Gln Tyr Ala Leu Glu Arg Gln Ile Arg
130 135 140
Gln Arg Ile Glu Thr Asp Leu Glu Glu Ser Arg Gln Thr Val Arg Asp
145 150 155 160
Val Gln Asn Asp Leu Ser Asp Val Gly Asn Arg Phe Ala Ala Ala Glu
165 170 175
Lys Gln Ile Ala His Leu Gln Glu Lys Glu Ala Glu Ala Glu Arg Leu
180 185 190
Arg Gln Ser His Thr Glu Leu Gln Glu Lys Ala Gln Gly Leu Ala Val
195 200 205
Glu Asn Glu Arg Leu Ala Thr Gln Ile Glu Gln Glu Arg Leu Ala Ser
210 215 220
Glu Glu Lys Leu Ser Leu Leu Gly Glu Ala Arg Lys Ser Leu Ser Asp
225 230 235 240
Gln Phe Gln Asn Leu Ala Asn Thr Ile Leu Glu Glu Lys Ser Arg Arg
245 250 255
Phe Thr Glu Gln Asn Arg Glu Gln Leu His Gln Val Leu Asn Pro Leu
260 265 270
Asn Glu Arg Ile His Gly Phe Gly Glu Leu Val Lys Gln Thr Tyr Asp
275 280 285
Lys Glu Ser Arg Glu Arg Leu Thr Leu Glu Asn Glu Leu Lys Arg Leu
290 295 300
Gln Gly Leu Asn Ala Gln Leu His Ser Glu Ala Lys Ala Leu Thr Asn
305 310 315 320
Ala Leu Thr Gly Thr Gln Asn Lys Val Gln Gly Asn Trp Gly Glu Met
325 330 335
Ile Leu Glu Thr Val Leu Glu Asn Ser Gly Leu Gln Lys Gly Arg Glu
340 345 350
Tyr Val Val Gln Ala Ala Ser Val Arg Lys Glu Glu Asp Gly Gly Thr
355 360 365
Arg Arg Leu Gln Pro Asp Val Leu Val Asn Leu Pro Asp Asn Lys Gln
370 375 380
Ile Val Ile Asp Ser Lys Val Ser Leu Thr Ala Tyr Val Arg Tyr Thr
385 390 395 400
Gln Ala Ala Asp Ala Asp Thr Ala Ala Arg Glu Leu Ala Ala His Val
405 410 415
Ala Ser Ile Arg Ala His Met Lys Gly Leu Ser Leu Lys Asp Tyr Thr
420 425 430
Asp Leu Glu Gly Val Asn Thr Leu Asp Phe Val Phe Met Phe Ile Pro
435 440 445
Val Glu Pro Ala Tyr Leu Leu Ala Leu Gln Asn Asp Ala Gly Leu Phe
450 455 460
Gln Glu Cys Phe Asp Lys Arg Ile Met Leu Val Gly Pro Ser Thr Leu
465 470 475 480
Leu Ala Thr Leu Arg Thr Val Ala Asn Ile Trp Arg Asn Glu Gln Gln
485 490 495
Asn Gln Asn Ala Leu Ala Ile Ala Asp Glu Gly Gly Lys Leu Tyr Asp
500 505 510
Lys Phe Val Gly Phe Val Gln Thr Leu Glu Ser Val Gly Lys Gly Ile
515 520 525
Asp Gln Ala Gln Ser Ser Phe Gln Thr Ala Phe Lys Gln Leu Ala Glu
530 535 540
Gly Arg Gly Asn Leu Val Gly Arg Ala Glu Lys Leu Arg Leu Leu Gly
545 550 555 560
Val Lys Ala Gly Lys Gln Leu Gln Arg Asp Leu Val Glu Arg Ser Asn
565 570 575
Glu Thr Thr Ala Leu Ser Glu Ser Leu Glu Tyr Ala Ala Glu Asp Glu
580 585 590
Ala Val
<210> 15
<211> 561
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1335 DNA sequence
<400> 15
atgaacagac tgctactgct gtctgccgcc gtcctgctga ctgcctgcgg cagcggcgaa 60
accgataaaa tcggacgggc aagtaccgtt ttcaacatac tgggcaaaaa cgaccgtatc 120
gaagtggaag gattcgacga tcccgacgtt caaggggttg cctgttatat ttcgtatgca 180
aaaaaaggcg gcttgaagga aatggtcaat ttggaagagg acgcgtccga cgcatcggtt 240
tcgtgcgttc agacggcatc ttcgatttct tttgacgaaa ccgccgtgcg caaaccgaaa 300
gaagttttca aacacggtgc gagcttcgcg ttcaagagcc ggcagattgt ccgttattac 360
gaccccaaac gcaaaacctt cgcctatttg gtgtacagcg ataaaatcat ccaaggctcg 420
ccgaaaaatt ccttaagcgc ggtttcctgt ttcggcggcg gcataccgca aaccgatggg 480
gtgcaagccg atacttccgg caacctgctt gccggcgcct gcatgatttc caacccgata 540
gaaaatctcg acaaacgctg a 561
<210> 16
<211> 186
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1335 protein sequence
<400> 16
Met Asn Arg Leu Leu Leu Leu Ser Ala Ala Val Leu Leu Thr Ala Cys
1 5 10 15
Gly Ser Gly Glu Thr Asp Lys Ile Gly Arg Ala Ser Thr Val Phe Asn
20 25 30
Ile Leu Gly Lys Asn Asp Arg Ile Glu Val Glu Gly Phe Asp Asp Pro
35 40 45
Asp Val Gln Gly Val Ala Cys Tyr Ile Ser Tyr Ala Lys Lys Gly Gly
50 55 60
Leu Lys Glu Met Val Asn Leu Glu Glu Asp Ala Ser Asp Ala Ser Val
65 70 75 80
Ser Cys Val Gln Thr Ala Ser Ser Ile Ser Phe Asp Glu Thr Ala Val
85 90 95
Arg Lys Pro Lys Glu Val Phe Lys His Gly Ala Ser Phe Ala Phe Lys
100 105 110
Ser Arg Gln Ile Val Arg Tyr Tyr Asp Pro Lys Arg Lys Thr Phe Ala
115 120 125
Tyr Leu Val Tyr Ser Asp Lys Ile Ile Gln Gly Ser Pro Lys Asn Ser
130 135 140
Leu Ser Ala Val Ser Cys Phe Gly Gly Gly Ile Pro Gln Thr Asp Gly
145 150 155 160
Val Gln Ala Asp Thr Ser Gly Asn Leu Leu Ala Gly Ala Cys Met Ile
165 170 175
Ser Asn Pro Ile Glu Asn Leu Asp Lys Arg
180 185
<210> 17
<211> 693
<212> DNA
<213> Neisseria meningitidis serogroup B NMB2035 DNA sequence
<400> 17
atgaccgcct ttgtccacac cctttcagac ggcatggaac tgaccgtcga aatcaagcgc 60
cgtgccaaga aaaacctgat tatccgcccc gccggcacac ataccgtccg catcagcgtc 120
ccaccctgct tctccgtctc cgctctaaac cgctggctgt atgaaaacga agccgtcctg 180
cggcaaacac tggcgaaaac accgccgccg caaactgccg aaaaccggct gcccgaatcc 240
atcctcttcc acggcagaca gcttgccctc accgcccatc aagacacgca aatcctgctg 300
atgccgtctg aaatccgtgt tcccgaaggc gcacccgaaa aacagcttgc gctgctgcgg 360
gactttttgg aacggcaggc gcacagttac ctgattcccc gcctcgaacg ccacgcccgc 420
accacacaac tgttccccgc ctcctcctcg ctgacctctg ccaaaacctt ctggggcgtg 480
tgccgcaaaa ccacaggcat acgcttcaac tggcggctgg tcggcgcacc ggaatacgtt 540
gccgactatg tctgcataca cgaactctgc cacctcgccc atcccgacca cagccccgcc 600
ttttgggaac tgacccgccg cttcgccccc tacacgccca aagcgaaaca gtggctcaaa 660
atccacggca gggaactttt cgccttaggc tga 693
<210> 18
<211> 230
<212> PRT
<213> Neisseria meningitidis serogroup B NMB2035 protein sequence
<400> 18
Met Thr Ala Phe Val His Thr Leu Ser Asp Gly Met Glu Leu Thr Val
1 5 10 15
Glu Ile Lys Arg Arg Ala Lys Lys Asn Leu Ile Ile Arg Pro Ala Gly
20 25 30
Thr His Thr Val Arg Ile Ser Val Pro Pro Cys Phe Ser Val Ser Ala
35 40 45
Leu Asn Arg Trp Leu Tyr Glu Asn Glu Ala Val Leu Arg Gln Thr Leu
50 55 60
Ala Lys Thr Pro Pro Pro Gln Thr Ala Glu Asn Arg Leu Pro Glu Ser
65 70 75 80
Ile Leu Phe His Gly Arg Gln Leu Ala Leu Thr Ala His Gln Asp Thr
85 90 95
Gln Ile Leu Leu Met Pro Ser Glu Ile Arg Val Pro Glu Gly Ala Pro
100 105 110
Glu Lys Gln Leu Ala Leu Leu Arg Asp Phe Leu Glu Arg Gln Ala His
115 120 125
Ser Tyr Leu Ile Pro Arg Leu Glu Arg His Ala Arg Thr Thr Gln Leu
130 135 140
Phe Pro Ala Ser Ser Ser Leu Thr Ser Ala Lys Thr Phe Trp Gly Val
145 150 155 160
Cys Arg Lys Thr Thr Gly Ile Arg Phe Asn Trp Arg Leu Val Gly Ala
165 170 175
Pro Glu Tyr Val Ala Asp Tyr Val Cys Ile His Glu Leu Cys His Leu
180 185 190
Ala His Pro Asp His Ser Pro Ala Phe Trp Glu Leu Thr Arg Arg Phe
195 200 205
Ala Pro Tyr Thr Pro Lys Ala Lys Gln Trp Leu Lys Ile His Gly Arg
210 215 220
Glu Leu Phe Ala Leu Gly
225 230
<210> 19
<211> 1257
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1351 DNA sequence
<400> 19
atgaacgccg cacaactcga ccataccgcc aaagttttgg ctgaaatgct gactttcaaa 60
cagcctgccg atgccgtcct ctccgcctat ttccgcgaac acaaaaagct cggcagtcaa 120
gatcgccacg aaatcgccga aaccgccttt gccgcgctgc gccactatca aaaaatcagt 180
accgccctac gccgtccgca cgcgcagccg cgcaaagccg ctctcgccgc actggttctc 240
ggcagaagca ccaacatcag ccaaatcaaa gacctgcttg atgaagaaga aacagcgttc 300
ctcggcaatt tgaaagcccg taaaaccgag ttttcagaca gcctgaatac cgccgcagaa 360
ttgccgcaat ggctggtgga acaactgaaa cagcattggc gcgaagaaga aatcctcgct 420
ttcggccgca gcatcaacca gcctgccccg ctcgacatcc gcgtcaacac tttgaaaggc 480
aaacgcgata aagtgctgcc gctgttgcaa gccgaaagtg ccgatgcaga ggcaacgcct 540
tattcgcctt ggggcatccg cctgaaaaac aaaatcgcgc ttaacaaaca cgaactgttt 600
ttagacggca cactggaagt ccaagacgaa ggcagccagc tgcttgcctt attggtgggc 660
gcaaaacgag gcgaaatcat tgtcgatttc tgtgccggtg ccggcggtaa aaccttggct 720
gtcggtgcgc aaatggcgaa caaaggcaga atctacgcct tcgatatcgc cgaaaaacgc 780
cttgccaacc tcaaaccgcg tatgacccgc gccggactga ccaatatcca ccccgaacgc 840
atcggcagcg aacacgatgc ccgtatcgcc cgactggcag gcaaagccga ccgtgtgttg 900
gtggacgcgc cctgctccgg tttgggcact ttacgccgca atcccgacct caaataccgc 960
caatccgccg aaaccgtcgc caaccttttg gaacagcaac acagcatcct cgatgccgcc 1020
tccaaactgg taaaaccgca aggacgtttg gtgtacgcca cttgcagcat cctgcccgaa 1080
gaaaacgagc tgcaagtcga acgtttcctg tccgaacatc ccgaatttga acccgtcaac 1140
tgcgccgaac tgcttgccgg tttgaaaatc gatttggata ccggcaaata cctgcgcctc 1200
aactccgccc gacaccaaac cgacggcttc ttcgccgccg tattgcaacg caaataa 1257
<210> 20
<211> 418
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1351 protein sequence
<400> 20
Met Asn Ala Ala Gln Leu Asp His Thr Ala Lys Val Leu Ala Glu Met
1 5 10 15
Leu Thr Phe Lys Gln Pro Ala Asp Ala Val Leu Ser Ala Tyr Phe Arg
20 25 30
Glu His Lys Lys Leu Gly Ser Gln Asp Arg His Glu Ile Ala Glu Thr
35 40 45
Ala Phe Ala Ala Leu Arg His Tyr Gln Lys Ile Ser Thr Ala Leu Arg
50 55 60
Arg Pro His Ala Gln Pro Arg Lys Ala Ala Leu Ala Ala Leu Val Leu
65 70 75 80
Gly Arg Ser Thr Asn Ile Ser Gln Ile Lys Asp Leu Leu Asp Glu Glu
85 90 95
Glu Thr Ala Phe Leu Gly Asn Leu Lys Ala Arg Lys Thr Glu Phe Ser
100 105 110
Asp Ser Leu Asn Thr Ala Ala Glu Leu Pro Gln Trp Leu Val Glu Gln
115 120 125
Leu Lys Gln His Trp Arg Glu Glu Glu Ile Leu Ala Phe Gly Arg Ser
130 135 140
Ile Asn Gln Pro Ala Pro Leu Asp Ile Arg Val Asn Thr Leu Lys Gly
145 150 155 160
Lys Arg Asp Lys Val Leu Pro Leu Leu Gln Ala Glu Ser Ala Asp Ala
165 170 175
Glu Ala Thr Pro Tyr Ser Pro Trp Gly Ile Arg Leu Lys Asn Lys Ile
180 185 190
Ala Leu Asn Lys His Glu Leu Phe Leu Asp Gly Thr Leu Glu Val Gln
195 200 205
Asp Glu Gly Ser Gln Leu Leu Ala Leu Leu Val Gly Ala Lys Arg Gly
210 215 220
Glu Ile Ile Val Asp Phe Cys Ala Gly Ala Gly Gly Lys Thr Leu Ala
225 230 235 240
Val Gly Ala Gln Met Ala Asn Lys Gly Arg Ile Tyr Ala Phe Asp Ile
245 250 255
Ala Glu Lys Arg Leu Ala Asn Leu Lys Pro Arg Met Thr Arg Ala Gly
260 265 270
Leu Thr Asn Ile His Pro Glu Arg Ile Gly Ser Glu His Asp Ala Arg
275 280 285
Ile Ala Arg Leu Ala Gly Lys Ala Asp Arg Val Leu Val Asp Ala Pro
290 295 300
Cys Ser Gly Leu Gly Thr Leu Arg Arg Asn Pro Asp Leu Lys Tyr Arg
305 310 315 320
Gln Ser Ala Glu Thr Val Ala Asn Leu Leu Glu Gln Gln His Ser Ile
325 330 335
Leu Asp Ala Ala Ser Lys Leu Val Lys Pro Gln Gly Arg Leu Val Tyr
340 345 350
Ala Thr Cys Ser Ile Leu Pro Glu Glu Asn Glu Leu Gln Val Glu Arg
355 360 365
Phe Leu Ser Glu His Pro Glu Phe Glu Pro Val Asn Cys Ala Glu Leu
370 375 380
Leu Ala Gly Leu Lys Ile Asp Leu Asp Thr Gly Lys Tyr Leu Arg Leu
385 390 395 400
Asn Ser Ala Arg His Gln Thr Asp Gly Phe Phe Ala Ala Val Leu Gln
405 410 415
Arg Lys
<210> 21
<211> 1014
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1574 DNA sequence
<400> 21
atgcaagtct attacgataa agatgccgat ctgtccctaa tcaaaggcaa aaccgttgcc 60
atcatcggtt acggttcgca aggtcatgcc catgccgcca acctgaaaga ttcgggtgta 120
aacgtggtga ttggtctgcg ccaaggttct tcttggaaaa aagccgaagc agccggtcat 180
gtcgtcaaaa ccgttgctga agcgaccaaa gaagccgatg tcgttatgct gctgctgcct 240
gacgaaacca tgcctgccgt ctatcacgcc gaagttacag ccaatttgaa agaaggcgca 300
acgctggcat ttgcacacgg cttcaacgtg cactacaacc aaatcgttcc gcgtgccgac 360
ttggacgtga ttatggttgc ccccaaaggt ccgggccata ccgtacgcag tgaatacaaa 420
cgcggcggcg gcgtgccttc tctgattgcc gtttaccaag acaattccgg caaagccaaa 480
gacatcgccc tgtcttatgc ggctgccaac ggcggcacca aaggcggtgt gattgaaacc 540
actttccgcg aagaaaccga aaccgatctg ttcggcgaac aagccgtatt gtgcggcggc 600
gtggtcgagt tgatcaaggc gggttttgaa accctgaccg aagccggtta cgcgcctgaa 660
atggcttact tcgaatgtct gcacgaaatg aaactgatcg ttgacctgat tttcgaaggc 720
ggtattgcca atatgaacta ctccatttcc aacaatgcgg agtacggcga atacgttacc 780
ggccctgaag tggtcaatgc ttccagcaaa gaagccatgc gcaatgccct gaaacgcatt 840
caaaccggcg aatacgcaaa aatgtttatc caagagggta atgtcaacta tgcgtctatg 900
actgcccgcc gccgtctgaa tgccgaccac caagttgaaa aagtcggcgc acaactgcgt 960
gccatgatgc cttggattac tgccaacaaa ttggttgacc aagacaaaaa ctga 1014
<210> 22
<211> 337
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1574 protein sequence
<400> 22
Met Gln Val Tyr Tyr Asp Lys Asp Ala Asp Leu Ser Leu Ile Lys Gly
1 5 10 15
Lys Thr Val Ala Ile Ile Gly Tyr Gly Ser Gln Gly His Ala His Ala
20 25 30
Ala Asn Leu Lys Asp Ser Gly Val Asn Val Val Ile Gly Leu Arg Gln
35 40 45
Gly Ser Ser Trp Lys Lys Ala Glu Ala Ala Gly His Val Val Lys Thr
50 55 60
Val Ala Glu Ala Thr Lys Glu Ala Asp Val Val Met Leu Leu Leu Pro
65 70 75 80
Asp Glu Thr Met Pro Ala Val Tyr His Ala Glu Val Thr Ala Asn Leu
85 90 95
Lys Glu Gly Ala Thr Leu Ala Phe Ala His Gly Phe Asn Val His Tyr
100 105 110
Asn Gln Ile Val Pro Arg Ala Asp Leu Asp Val Ile Met Val Ala Pro
115 120 125
Lys Gly Pro Gly His Thr Val Arg Ser Glu Tyr Lys Arg Gly Gly Gly
130 135 140
Val Pro Ser Leu Ile Ala Val Tyr Gln Asp Asn Ser Gly Lys Ala Lys
145 150 155 160
Asp Ile Ala Leu Ser Tyr Ala Ala Ala Asn Gly Gly Thr Lys Gly Gly
165 170 175
Val Ile Glu Thr Thr Phe Arg Glu Glu Thr Glu Thr Asp Leu Phe Gly
180 185 190
Glu Gln Ala Val Leu Cys Gly Gly Val Val Glu Leu Ile Lys Ala Gly
195 200 205
Phe Glu Thr Leu Thr Glu Ala Gly Tyr Ala Pro Glu Met Ala Tyr Phe
210 215 220
Glu Cys Leu His Glu Met Lys Leu Ile Val Asp Leu Ile Phe Glu Gly
225 230 235 240
Gly Ile Ala Asn Met Asn Tyr Ser Ile Ser Asn Asn Ala Glu Tyr Gly
245 250 255
Glu Tyr Val Thr Gly Pro Glu Val Val Asn Ala Ser Ser Lys Glu Ala
260 265 270
Met Arg Asn Ala Leu Lys Arg Ile Gln Thr Gly Glu Tyr Ala Lys Met
275 280 285
Phe Ile Gln Glu Gly Asn Val Asn Tyr Ala Ser Met Thr Ala Arg Arg
290 295 300
Arg Leu Asn Ala Asp His Gln Val Glu Lys Val Gly Ala Gln Leu Arg
305 310 315 320
Ala Met Met Pro Trp Ile Thr Ala Asn Lys Leu Val Asp Gln Asp Lys
325 330 335
Asn
<210> 23
<211> 693
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1298 DNA sequence
<400> 23
atgaaactta tcaaatacct gcaatatcaa ggcataggaa gccgcaagca gtgccaatgg 60
ctgattgccg gcggttatgt tttcatcaac ggaacctgca tggacgacac cgatgcagac 120
atcgattcct catccgtcga aacgttggat attgacgggg aagcagtaac cgtcgttccc 180
gaaccctatt tctacatcat gctcaacaag cctgaagatt acgaaacttc gcacaaaccc 240
aagcactacc gcagcgtatt cagcctgttc cccgacaata tgcggaacat cgatatgcag 300
gcggtcggca ggctggatgc agatacgacc ggcgtattgc tgattaccaa cgacggcaaa 360
ctgaaccaca gcctgacttc gccgagcaga aaaattccca agctgtacga agtaacgctc 420
aaacacccca caggagaaac gctctgcgaa accttgaaaa acggcgtgct gctccacgac 480
gaaaacgaaa ccgtttgtgc cgccgatgcc gttttgaaaa acccgaccac cctgctgctg 540
accattaccg aaggaaaata ccaccaagtc aaacgcatga tcgccgccgc cggcaaccgc 600
gtgcaacacc ttcatcgccg gcgattcgca catctggaaa cagaaaacct caaacccggg 660
gaatggaaat ttatcgaatg tccaaaattc tga 693
<210> 24
<211> 230
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1298 protein sequence
<400> 24
Met Lys Leu Ile Lys Tyr Leu Gln Tyr Gln Gly Ile Gly Ser Arg Lys
1 5 10 15
Gln Cys Gln Trp Leu Ile Ala Gly Gly Tyr Val Phe Ile Asn Gly Thr
20 25 30
Cys Met Asp Asp Thr Asp Ala Asp Ile Asp Ser Ser Ser Val Glu Thr
35 40 45
Leu Asp Ile Asp Gly Glu Ala Val Thr Val Val Pro Glu Pro Tyr Phe
50 55 60
Tyr Ile Met Leu Asn Lys Pro Glu Asp Tyr Glu Thr Ser His Lys Pro
65 70 75 80
Lys His Tyr Arg Ser Val Phe Ser Leu Phe Pro Asp Asn Met Arg Asn
85 90 95
Ile Asp Met Gln Ala Val Gly Arg Leu Asp Ala Asp Thr Thr Gly Val
100 105 110
Leu Leu Ile Thr Asn Asp Gly Lys Leu Asn His Ser Leu Thr Ser Pro
115 120 125
Ser Arg Lys Ile Pro Lys Leu Tyr Glu Val Thr Leu Lys His Pro Thr
130 135 140
Gly Glu Thr Leu Cys Glu Thr Leu Lys Asn Gly Val Leu Leu His Asp
145 150 155 160
Glu Asn Glu Thr Val Cys Ala Ala Asp Ala Val Leu Lys Asn Pro Thr
165 170 175
Thr Leu Leu Leu Thr Ile Thr Glu Gly Lys Tyr His Gln Val Lys Arg
180 185 190
Met Ile Ala Ala Ala Gly Asn Arg Val Gln His Leu His Arg Arg Arg
195 200 205
Phe Ala His Leu Glu Thr Glu Asn Leu Lys Pro Gly Glu Trp Lys Phe
210 215 220
Ile Glu Cys Pro Lys Phe
225 230
<210> 25
<211> 900
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1856 DNA sequence
<400> 25
atgaaaacca attcagaaga actgaccgta tttgttcaag tggtggaaag cggcagcttc 60
agccgtgcgg cggagcagtt ggcgatggca aattctgccg taagccgcat cgtcaaacgg 120
ctggaggaaa agttgggtgt gaacctgctc aaccgcacca cgcggcaact cagtctgacg 180
gaagaaggcg cgcaatattt ccgccgcgcg cagagaatcc tgcaagaaat ggcagcggcg 240
gaaaccgaaa tgctggcagt gcacgaaata ccgcaaggcg tgttgagcgt ggattccgcg 300
atgccgatgg tgctgcatct gctggcgccg ctggcagcaa aattcaacga acgctatccg 360
catatccgac tttcgctcgt ttcttccgaa ggctatatca atctgattga acgcaaagtc 420
gatattgcct tacgggccgg agaattggac gattccgggc tgcgtgcacg ccatctgttt 480
gacagccgct tccgcgtaat cgccagtcct gaatacctgg caaaacacgg cacgccgcaa 540
tctacagaag agcttgccgg ccaccaatgt ttaggcttca ccgaacccgg ttctctaaat 600
acatgggcgg ttttagatgc gcagggaaat ccctataaga tttcaccgca ctttaccgcc 660
agcagcggtg aaatcttacg ctcgttgtgc ctttcaggtt gcggtattgt ttgcttatca 720
gattttttgg ttgacaacga catcgctgaa ggaaagttaa ttcccctgct cgccgaacaa 780
acctccgata aaacacaccc ctttaatgct gtttattaca gcgataaagc cgtcaatctc 840
cgcttacgcg tatttttgga ttttttagtg gaggaactgg gaaacaatct ctgtggataa 900
<210> 26
<211> 299
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1856 protein sequence
<400> 26
Met Lys Thr Asn Ser Glu Glu Leu Thr Val Phe Val Gln Val Val Glu
1 5 10 15
Ser Gly Ser Phe Ser Arg Ala Ala Glu Gln Leu Ala Met Ala Asn Ser
20 25 30
Ala Val Ser Arg Ile Val Lys Arg Leu Glu Glu Lys Leu Gly Val Asn
35 40 45
Leu Leu Asn Arg Thr Thr Arg Gln Leu Ser Leu Thr Glu Glu Gly Ala
50 55 60
Gln Tyr Phe Arg Arg Ala Gln Arg Ile Leu Gln Glu Met Ala Ala Ala
65 70 75 80
Glu Thr Glu Met Leu Ala Val His Glu Ile Pro Gln Gly Val Leu Ser
85 90 95
Val Asp Ser Ala Met Pro Met Val Leu His Leu Leu Ala Pro Leu Ala
100 105 110
Ala Lys Phe Asn Glu Arg Tyr Pro His Ile Arg Leu Ser Leu Val Ser
115 120 125
Ser Glu Gly Tyr Ile Asn Leu Ile Glu Arg Lys Val Asp Ile Ala Leu
130 135 140
Arg Ala Gly Glu Leu Asp Asp Ser Gly Leu Arg Ala Arg His Leu Phe
145 150 155 160
Asp Ser Arg Phe Arg Val Ile Ala Ser Pro Glu Tyr Leu Ala Lys His
165 170 175
Gly Thr Pro Gln Ser Thr Glu Glu Leu Ala Gly His Gln Cys Leu Gly
180 185 190
Phe Thr Glu Pro Gly Ser Leu Asn Thr Trp Ala Val Leu Asp Ala Gln
195 200 205
Gly Asn Pro Tyr Lys Ile Ser Pro His Phe Thr Ala Ser Ser Gly Glu
210 215 220
Ile Leu Arg Ser Leu Cys Leu Ser Gly Cys Gly Ile Val Cys Leu Ser
225 230 235 240
Asp Phe Leu Val Asp Asn Asp Ile Ala Glu Gly Lys Leu Ile Pro Leu
245 250 255
Leu Ala Glu Gln Thr Ser Asp Lys Thr His Pro Phe Asn Ala Val Tyr
260 265 270
Tyr Ser Asp Lys Ala Val Asn Leu Arg Leu Arg Val Phe Leu Asp Phe
275 280 285
Leu Val Glu Glu Leu Gly Asn Asn Leu Cys Gly
290 295
<210> 27
<211> 696
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0119 DNA sequence
<400> 27
atgatgaagg atttgaattt gagcaacagc ctgttcaaag gctacaacga caaacatggc 60
ttaatgattt gtggctatga atggggttgg agtaaagccg atgaggctgc ttatgtagca 120
ggtgaataca aactccctga aaacaaaatc gaccatacat ttgcaaacaa atccctctat 180
ttcggagagc aggcaaaaaa gtggcgttac gacaatacga taaaaaattg gtttgaaatg 240
tggggacacc ccttagacga aaatggattg ggcggtgcat ttgaaaaatc cctggttcaa 300
accaactggg ctgctacaca gggcaacact atcgacaatc ccgacaagtt cacacaaccc 360
gagcacatcg ataattttct ctaccacatc gaaaaactgc gtccgaaagt catcctcttc 420
atgggcagca ggttggcgga ttttctgaac aaccaaaatg tactgccacg cttcgagcag 480
ttggtcggta agcagaccaa accgctggag acggtgcaaa aagaatttga cggtacacgt 540
ttcaatgtca aattccaatc gtttgaagat tgcgaagtcg tctgctttcc ccatcccagt 600
gccagtcgcg gtctatctta cgattacatc gccttgtttg cgcctgaaat gaaccggatt 660
ttatcggact ttaaaacaac acgcggattc aaataa 696
<210> 28
<211> 231
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0119 protein sequence
<400> 28
Met Met Lys Asp Leu Asn Leu Ser Asn Ser Leu Phe Lys Gly Tyr Asn
1 5 10 15
Asp Lys His Gly Leu Met Ile Cys Gly Tyr Glu Trp Gly Trp Ser Lys
20 25 30
Ala Asp Glu Ala Ala Tyr Val Ala Gly Glu Tyr Lys Leu Pro Glu Asn
35 40 45
Lys Ile Asp His Thr Phe Ala Asn Lys Ser Leu Tyr Phe Gly Glu Gln
50 55 60
Ala Lys Lys Trp Arg Tyr Asp Asn Thr Ile Lys Asn Trp Phe Glu Met
65 70 75 80
Trp Gly His Pro Leu Asp Glu Asn Gly Leu Gly Gly Ala Phe Glu Lys
85 90 95
Ser Leu Val Gln Thr Asn Trp Ala Ala Thr Gln Gly Asn Thr Ile Asp
100 105 110
Asn Pro Asp Lys Phe Thr Gln Pro Glu His Ile Asp Asn Phe Leu Tyr
115 120 125
His Ile Glu Lys Leu Arg Pro Lys Val Ile Leu Phe Met Gly Ser Arg
130 135 140
Leu Ala Asp Phe Leu Asn Asn Gln Asn Val Leu Pro Arg Phe Glu Gln
145 150 155 160
Leu Val Gly Lys Gln Thr Lys Pro Leu Glu Thr Val Gln Lys Glu Phe
165 170 175
Asp Gly Thr Arg Phe Asn Val Lys Phe Gln Ser Phe Glu Asp Cys Glu
180 185 190
Val Val Cys Phe Pro His Pro Ser Ala Ser Arg Gly Leu Ser Tyr Asp
195 200 205
Tyr Ile Ala Leu Phe Ala Pro Glu Met Asn Arg Ile Leu Ser Asp Phe
210 215 220
Lys Thr Thr Arg Gly Phe Lys
225 230
<210> 29
<211> 1065
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1705 DNA sequence
<400> 29
atggaaaaag aattcaggat attaaatatc gtatcggcca agatttgggg tggaggcgaa 60
caatatgtct atgatgtttc aaaagcattg gggcttcggg gctgcacaat gtttaccgcc 120
gtcaataaaa ataatgaatt gatgcacagg cgattttccg aagtttcttc cgttttcaca 180
acgcgccttc acacgctcaa cgggctgttt tcgctctacg cacttacccg ctttatccgg 240
aaaaaccgca tttcccacct gatgatacac accggcaaaa ttgccgcctt atccatactt 300
ttgaaaaaac tgaccggggt gcgcctgata tttgtcaaac ataatgtcgt cgccaacaaa 360
accgattttt accaccgcct gatacagaaa aacacagacc gctttatttg cgtttcccgt 420
ctggtttacg atgtgcaaac cgccgacaat ccctttaaag aaaaataccg gattgttcat 480
aacggtatcg ataccggccg tttccctccc tctcaagaaa aacccgacag ccgttttttt 540
accgtcgcct acgccggcag gatcagtcca gaaaaaggat tggaaaacct gattgaagcc 600
tgtgtgatac tgcatcggaa atatcctcaa atcaggctca aattggcagg ggacggacat 660
ccggattata tgtgccgcct gaagcgggac gtatctgctt caggagcaga accatttgtt 720
tcttttgaag ggtttaccga aaaacttgct tcgttttacc gccaaagcga tgtcgtggtt 780
ttgcccagcc tcgtcccgga ggcattcggt ttgtcattat gcgaggcgat gtactgccga 840
acggcggtga tttccaatac tttgggggcg caaaaggaaa ttgtcgaaca tcatcaatcg 900
gggattctgc tggacaggct gacacctgaa tctttggcgg acgaaatcga acgcctcgtc 960
ttgaaccctg aaacgaaaaa cgcactggca acggcagctc atcaatgcgt cgccgcccgt 1020
tttaccatca accataccgc cgacaaatta ttggatgcaa tataa 1065
<210> 30
<211> 354
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1705 protein sequence
<400> 30
Met Glu Lys Glu Phe Arg Ile Leu Asn Ile Val Ser Ala Lys Ile Trp
1 5 10 15
Gly Gly Gly Glu Gln Tyr Val Tyr Asp Val Ser Lys Ala Leu Gly Leu
20 25 30
Arg Gly Cys Thr Met Phe Thr Ala Val Asn Lys Asn Asn Glu Leu Met
35 40 45
His Arg Arg Phe Ser Glu Val Ser Ser Val Phe Thr Thr Arg Leu His
50 55 60
Thr Leu Asn Gly Leu Phe Ser Leu Tyr Ala Leu Thr Arg Phe Ile Arg
65 70 75 80
Lys Asn Arg Ile Ser His Leu Met Ile His Thr Gly Lys Ile Ala Ala
85 90 95
Leu Ser Ile Leu Leu Lys Lys Leu Thr Gly Val Arg Leu Ile Phe Val
100 105 110
Lys His Asn Val Val Ala Asn Lys Thr Asp Phe Tyr His Arg Leu Ile
115 120 125
Gln Lys Asn Thr Asp Arg Phe Ile Cys Val Ser Arg Leu Val Tyr Asp
130 135 140
Val Gln Thr Ala Asp Asn Pro Phe Lys Glu Lys Tyr Arg Ile Val His
145 150 155 160
Asn Gly Ile Asp Thr Gly Arg Phe Pro Pro Ser Gln Glu Lys Pro Asp
165 170 175
Ser Arg Phe Phe Thr Val Ala Tyr Ala Gly Arg Ile Ser Pro Glu Lys
180 185 190
Gly Leu Glu Asn Leu Ile Glu Ala Cys Val Ile Leu His Arg Lys Tyr
195 200 205
Pro Gln Ile Arg Leu Lys Leu Ala Gly Asp Gly His Pro Asp Tyr Met
210 215 220
Cys Arg Leu Lys Arg Asp Val Ser Ala Ser Gly Ala Glu Pro Phe Val
225 230 235 240
Ser Phe Glu Gly Phe Thr Glu Lys Leu Ala Ser Phe Tyr Arg Gln Ser
245 250 255
Asp Val Val Val Leu Pro Ser Leu Val Pro Glu Ala Phe Gly Leu Ser
260 265 270
Leu Cys Glu Ala Met Tyr Cys Arg Thr Ala Val Ile Ser Asn Thr Leu
275 280 285
Gly Ala Gln Lys Glu Ile Val Glu His His Gln Ser Gly Ile Leu Leu
290 295 300
Asp Arg Leu Thr Pro Glu Ser Leu Ala Asp Glu Ile Glu Arg Leu Val
305 310 315 320
Leu Asn Pro Glu Thr Lys Asn Ala Leu Ala Thr Ala Ala His Gln Cys
325 330 335
Val Ala Ala Arg Phe Thr Ile Asn His Thr Ala Asp Lys Leu Leu Asp
340 345 350
Ala Ile
<210> 31
<211> 1272
<212> DNA
<213> Neisseria meningitidis serogroup B NMB2065 DNA sequence
<400> 31
atgcaggaac agaatcggaa accaagtttt cccatagtga tgttgctggt gtcggttgcc 60
ctgtggatag cgtctttatc caatgttgca ttttatttgg gcaatcatgg aagcatggag 120
ggtttgaccg ttttgatttt ggggtcgata tttgcttctt tggatatcag gtattgtgcg 180
gtctatgcga attatgtttg gttggcggcc attgttttgc tggcgttgcg gaagaaggtc 240
gtgcctgtcc atgcggcact ttggggcttg gcgttggtgg ctttcagtgt gaaagccgta 300
tacgtcgatg aagcagggaa tacatcggat attgtgcgct acggtgcagg attttatttg 360
tggtatgccg catttgcggt tgccaccatc ggtacgtttg ccggaaagaa taaggaaaga 420
aaagccgcat cagcggcaga cgggataaaa atgacgtttg ataaatggtt gggcttgtca 480
aaactgccta aaaatgaagc aagaatgctg ctacaatatg tttcggaata tacgcgcgtg 540
cagttgttga cgcggggcgg ggaagaaatg ccggacgaag tccgacagcg ggcggacagg 600
ctggcgcaac gccgtctgaa cggcgagccg gttgcctata ttttaggtgt gcgcgaattt 660
tatggcagac gctttacagt caatccgagc gtgctgattc cgcgccccga aaccgaacat 720
ttggtcgaag ccgtattggc gcgcctgccc gaaaacgggc gcgtgtggga tttggggacg 780
ggcagcggcg cggttgccgt aaccgtcgcg ctcgaacgcc ccgatgcgtt tgtgcgcgca 840
tccgacatca gcccgcccgc ccttgaaacg gcgcggaaaa atgcggcgga tttgggcgcg 900
cgggtcgaat ttgcacacgg ttcgtggttc gacaccgata tgccgtctga agggaaatgg 960
gacatcatcg tgtccaaccc gccctatatc gaaaacggcg ataaacattt gttgcaaggc 1020
gatttgcggt ttgagccgca aatcgcgctg accgactttt cagacggcct aagctgcatc 1080
cgcaccttgg cgcaaggcgc gcccgaccgt ttggcggaag gcggtttttt attgctggaa 1140
cacggtttcg atcagggcgc ggcggtgcgc ggcgtgttgg cggagaatgg tttttcagga 1200
gtggaaaccc tgccggattt ggcgggtttg gacagggtta cgctggggaa gtatatgaag 1260
catttgaaat aa 1272
<210> 32
<211> 423
<212> PRT
<213> Neisseria meningitidis serogroup B NMB2065 protein sequence
<400> 32
Met Gln Glu Gln Asn Arg Lys Pro Ser Phe Pro Ile Val Met Leu Leu
1 5 10 15
Val Ser Val Ala Leu Trp Ile Ala Ser Leu Ser Asn Val Ala Phe Tyr
20 25 30
Leu Gly Asn His Gly Ser Met Glu Gly Leu Thr Val Leu Ile Leu Gly
35 40 45
Ser Ile Phe Ala Ser Leu Asp Ile Arg Tyr Cys Ala Val Tyr Ala Asn
50 55 60
Tyr Val Trp Leu Ala Ala Ile Val Leu Leu Ala Leu Arg Lys Lys Val
65 70 75 80
Val Pro Val His Ala Ala Leu Trp Gly Leu Ala Leu Val Ala Phe Ser
85 90 95
Val Lys Ala Val Tyr Val Asp Glu Ala Gly Asn Thr Ser Asp Ile Val
100 105 110
Arg Tyr Gly Ala Gly Phe Tyr Leu Trp Tyr Ala Ala Phe Ala Val Ala
115 120 125
Thr Ile Gly Thr Phe Ala Gly Lys Asn Lys Glu Arg Lys Ala Ala Ser
130 135 140
Ala Ala Asp Gly Ile Lys Met Thr Phe Asp Lys Trp Leu Gly Leu Ser
145 150 155 160
Lys Leu Pro Lys Asn Glu Ala Arg Met Leu Leu Gln Tyr Val Ser Glu
165 170 175
Tyr Thr Arg Val Gln Leu Leu Thr Arg Gly Gly Glu Glu Met Pro Asp
180 185 190
Glu Val Arg Gln Arg Ala Asp Arg Leu Ala Gln Arg Arg Leu Asn Gly
195 200 205
Glu Pro Val Ala Tyr Ile Leu Gly Val Arg Glu Phe Tyr Gly Arg Arg
210 215 220
Phe Thr Val Asn Pro Ser Val Leu Ile Pro Arg Pro Glu Thr Glu His
225 230 235 240
Leu Val Glu Ala Val Leu Ala Arg Leu Pro Glu Asn Gly Arg Val Trp
245 250 255
Asp Leu Gly Thr Gly Ser Gly Ala Val Ala Val Thr Val Ala Leu Glu
260 265 270
Arg Pro Asp Ala Phe Val Arg Ala Ser Asp Ile Ser Pro Pro Ala Leu
275 280 285
Glu Thr Ala Arg Lys Asn Ala Ala Asp Leu Gly Ala Arg Val Glu Phe
290 295 300
Ala His Gly Ser Trp Phe Asp Thr Asp Met Pro Ser Glu Gly Lys Trp
305 310 315 320
Asp Ile Ile Val Ser Asn Pro Pro Tyr Ile Glu Asn Gly Asp Lys His
325 330 335
Leu Leu Gln Gly Asp Leu Arg Phe Glu Pro Gln Ile Ala Leu Thr Asp
340 345 350
Phe Ser Asp Gly Leu Ser Cys Ile Arg Thr Leu Ala Gln Gly Ala Pro
355 360 365
Asp Arg Leu Ala Glu Gly Gly Phe Leu Leu Leu Glu His Gly Phe Asp
370 375 380
Gln Gly Ala Ala Val Arg Gly Val Leu Ala Glu Asn Gly Phe Ser Gly
385 390 395 400
Val Glu Thr Leu Pro Asp Leu Ala Gly Leu Asp Arg Val Thr Leu Gly
405 410 415
Lys Tyr Met Lys His Leu Lys
420
<210> 33
<211> 1170
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0339 DNA sequence
<400> 33
atggacaacg aattgtggat tatcctgctg ccgattatcc ttttgcccgt cttcttcgcg 60
atgggctggt ttgccgcccg cgtggatatg aaaaccgtat tgaagcaggc aaaaagcatc 120
ccttcgggat tttataaaag cttggacgct ttggtcgacc gcaacagcgg gcgcgcggca 180
agggagttgg cggaagtcgt cgacggccgg ccgcaatcgt atgatttgaa cctcaccctc 240
ggcaaacttt accgccagcg tggcgaaaac gacaaagcca tcaacataca ccggacaatg 300
ctcgattctc ccgatacggt cggcgaaaag cgcgcgcgcg tcctgtttga attggcgcaa 360
aactaccaaa gtgcggggtt ggtcgatcgt gccgaacaga tttttttggg gctgcaagac 420
ggtaaaatgg cgcgtgaagc cagacagcac ctgctcaata tctaccaaca ggacagggat 480
tgggaaaaag cggttgaaac cgcccggctg ctcagccatg acgatcagac ctatcagttt 540
gaaatcgccc agttttattg cgaacttgcc caagccgcgc tgttcaagtc caatttcgat 600
gtcgcgcgtt tcaatgtcgg caaggcactc gaagccaaca aaaaatgcac ccgcgccaac 660
atgattttgg gcgacatcga acaccgacaa ggcaatttcc ctgccgccgt cgaagcctat 720
gccgccatcg agcagcaaaa ccatgcatac ttgagcatgg tcggcgagaa gctttacgaa 780
gcctatgccg cgcagggaaa acctgaagaa ggcttgaacc gtctgacagg atatatgcag 840
acgtttcccg aacttgacct gatcaatgtc gtgtacgaga aatccctgct gcttaagtgc 900
gagaaagaag ccgcgcaaac cgccgtcgag cttgtccgcc gcaagcccga ccttaacggc 960
gtgtaccgcc tgctcggttt gaaactcagc gatatgaatc cggcttggaa agccgatgcc 1020
gacatgatgc gttcggttat cggacggcag ctacagcgca gcgtgatgta ccgttgccgc 1080
aactgccact tcaaatccca agtctttttc tggcactgcc ccgcctgcaa caaatggcag 1140
acgtttaccc cgaataaaat cgaagtttaa 1170
<210> 34
<211> 389
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0339 protein sequence
<400> 34
Met Asp Asn Glu Leu Trp Ile Ile Leu Leu Pro Ile Ile Leu Leu Pro
1 5 10 15
Val Phe Phe Ala Met Gly Trp Phe Ala Ala Arg Val Asp Met Lys Thr
20 25 30
Val Leu Lys Gln Ala Lys Ser Ile Pro Ser Gly Phe Tyr Lys Ser Leu
35 40 45
Asp Ala Leu Val Asp Arg Asn Ser Gly Arg Ala Ala Arg Glu Leu Ala
50 55 60
Glu Val Val Asp Gly Arg Pro Gln Ser Tyr Asp Leu Asn Leu Thr Leu
65 70 75 80
Gly Lys Leu Tyr Arg Gln Arg Gly Glu Asn Asp Lys Ala Ile Asn Ile
85 90 95
His Arg Thr Met Leu Asp Ser Pro Asp Thr Val Gly Glu Lys Arg Ala
100 105 110
Arg Val Leu Phe Glu Leu Ala Gln Asn Tyr Gln Ser Ala Gly Leu Val
115 120 125
Asp Arg Ala Glu Gln Ile Phe Leu Gly Leu Gln Asp Gly Lys Met Ala
130 135 140
Arg Glu Ala Arg Gln His Leu Leu Asn Ile Tyr Gln Gln Asp Arg Asp
145 150 155 160
Trp Glu Lys Ala Val Glu Thr Ala Arg Leu Leu Ser His Asp Asp Gln
165 170 175
Thr Tyr Gln Phe Glu Ile Ala Gln Phe Tyr Cys Glu Leu Ala Gln Ala
180 185 190
Ala Leu Phe Lys Ser Asn Phe Asp Val Ala Arg Phe Asn Val Gly Lys
195 200 205
Ala Leu Glu Ala Asn Lys Lys Cys Thr Arg Ala Asn Met Ile Leu Gly
210 215 220
Asp Ile Glu His Arg Gln Gly Asn Phe Pro Ala Ala Val Glu Ala Tyr
225 230 235 240
Ala Ala Ile Glu Gln Gln Asn His Ala Tyr Leu Ser Met Val Gly Glu
245 250 255
Lys Leu Tyr Glu Ala Tyr Ala Ala Gln Gly Lys Pro Glu Glu Gly Leu
260 265 270
Asn Arg Leu Thr Gly Tyr Met Gln Thr Phe Pro Glu Leu Asp Leu Ile
275 280 285
Asn Val Val Tyr Glu Lys Ser Leu Leu Leu Lys Cys Glu Lys Glu Ala
290 295 300
Ala Gln Thr Ala Val Glu Leu Val Arg Arg Lys Pro Asp Leu Asn Gly
305 310 315 320
Val Tyr Arg Leu Leu Gly Leu Lys Leu Ser Asp Met Asn Pro Ala Trp
325 330 335
Lys Ala Asp Ala Asp Met Met Arg Ser Val Ile Gly Arg Gln Leu Gln
340 345 350
Arg Ser Val Met Tyr Arg Cys Arg Asn Cys His Phe Lys Ser Gln Val
355 360 365
Phe Phe Trp His Cys Pro Ala Cys Asn Lys Trp Gln Thr Phe Thr Pro
370 375 380
Asn Lys Ile Glu Val
385
<210> 35
<211> 3606
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0401 DNA sequence
<400> 35
atgtttcatt ttgcatttcc ggcacaaact gccctgcgcc aagcgataac cgatgcctac 60
cgccgtaatg aaatcgaagc cgtacaggat atgttgcaac gtgcacagat gagcgacgaa 120
gagcgcaacg ccgcctccga gcttgcccgc cgtttggtta cccaagtccg cgccggccgc 180
accaaagccg gcggcgtgga tgcgctgatg cacgagtttt cactctccag cgaagaaggc 240
atcgcgctga tgtgtctggc agaagccctg ctgcgtatcc ccgacaacgc cacgcgcgac 300
cgcctgattg ccgacaagat ttcagacggc aactggaaaa gccatttgaa caacagccct 360
tccctcttcg tcaatgctgc cgcctggggc ctgctgatta ccggcaaact gaccgccaca 420
aacgacaaac aaatgagttc cgcactcagc cgcctgatca gcaaaggcgg cgcaccgctc 480
atccgccaag gcgtaaatta cgccatgcgg cttctgggca aacagttcgt aaccggacag 540
accattgaag aagccctgca aaacggcaaa gaacgcgaaa aaatgggcta ccgcttctcc 600
ttcgatatgt tgggcgaagc cgcctacacc caagccgatg ccgaccgcta ctaccgcgac 660
tatgtcgaag ccatccacgc catcggcaaa gatgcggcag gacaaggcgt ttacgaaggt 720
aacggtattt ccgtcaaact ttccgccatc catccgcgct actcgcgcac ccaacacggc 780
cgcgtgatgg gcgaactgtt gccgcgcctg aaagagctgt tccttttggg taaaaaatac 840
gatatcggta tcaacatcga tgccgaagaa gccaaccgtc tggagctgtc tttggatttg 900
atggaggctt tggtttcaga ccctgacttg gctggctaca aaggtatcgg tttcgttgtc 960
caagcctacc aaaaacgttg tccgttcgtt atcgactacc tgatcgacct tgcccgccgc 1020
aacaaccaaa aactaatgat ccgcctcgtc aaaggcgcgt attgggacag cgaaatcaaa 1080
tgggcgcaag tggacggctt gaacggctat ccgacctaca cccgcaaagt ccacaccgac 1140
atctcctacc tcgcctgcgc gcgcaaactg ctttccgcgc aagacgcggt attcccgcaa 1200
tttgccaccc acaacgccta cactttgggc gcaatctacc aaatgggtaa aggcaaagat 1260
tttgaacacc aatgcctgca cggtatgggc gaaaccctgt acgaccaagt cgtcggcccg 1320
caaaacttag gccgccgcgt gcgcgtgtac gccccagtcg gcacacacga aaccctgctc 1380
gcctacttgg tgcgccgcct gttggaaaac ggcgcgaact cgtctttcgt caaccaaatc 1440
gtcgatgaaa acatcagcat cgacacgctc atccgcagcc cgttcgacac catcgccgaa 1500
caaggcatcc acctgcacaa cgccctgccg ctgccgcgcg atttgtacgg caaatgccgt 1560
ctgaactcgc aaggcgtgga cttgagcaac gaaaacgtat tgcagcagct tcaagaacag 1620
atgaacaaag ccgccgcgca agacttccac gccgcatcca tcgtcaacgg caaagcccgc 1680
gatgtcggcg aagcgcaacc gattaaaaac cctgccgacc acgacgacat cgtcggcaca 1740
gtcagctttg ccgatgccgc gcttgcccaa gaagcggttg gcgcagccgt tgccgcgttc 1800
cccgaatgga gtgcgacacc tgccgccgaa cgcgccgcct gcctgcgccg ttttgccgat 1860
ttgctggagc agcacacccc agcactgatg atgcttgccg tgcgcgaagc aggcaaaacg 1920
ctgaacaacg ccattgccga agtgcgcgaa gccgtcgatt tctgccgcta ctacgcaaac 1980
gaagccgaac ataccctgcc tcaagacgca aaagccgtcg gcgcgattgt cgccatcagc 2040
ccgtggaact tcccgctcgc catctttacc ggcgaagtcg tttccgcatt ggcggcaggc 2100
aacaccgtca tcgccaaacc cgccgaacaa accagcctga ttgccggtta tgccgtttcc 2160
ctcatgcacg aagccggcat cccgacttcc gccctgcaac tcgtcctcgg cgcaggcgac 2220
gtgggtgcgg cattgaccaa cgatgcccgc atcggcggcg tgattttcac cggctcgacc 2280
gaagtggcgc gcctgatcaa caaagccctt gccaaacgcg gcgacaatcc cgtcctgatt 2340
gccgaaaccg gcggacaaaa cgccatgatt gtcgattcca ccgcacttgc cgagcaagtc 2400
tgcgccgacg tattgaactc cgccttcgac agcgcgggac aacgctgctc cgccctgcgc 2460
attttgtgcg tccaagaaga cgttgccgac cgtatgctcg acatgatcaa aggcgctatg 2520
gacgaactcg tcgtcggcaa accgattcag ctcactaccg atgtcggccc cgtcatcgat 2580
gccgaagcac agcaaaacct gttgaaccac atcaacaaaa tgaaaggtgt tgccaagtcc 2640
taccacgaag tcaaaaccgc cgccgatgtc gattccaaaa aatccacgtt cgttcgcccc 2700
atcctgtttg aattgaacaa cctcaacgaa ctgcaacgcg aagtcttcgg tcccgtcctg 2760
cacgtcgtcc gctaccgcgc cgacgaactc gacaacgtca tcgaccaaat caacagcaaa 2820
ggctacgccc tgacccacgg cgtacacagc cgcatcgaag gcacggtacg ccacatccgc 2880
agccgcatcg aagccggcaa cgtttacgtc aaccgcaaca tcgtcggcgc agtcgtcggc 2940
gtacagccct tcggcggaca cggtctgtcc ggcacaggcc ccaaagcagg cggttcgttc 3000
tacctgcaaa aactgacccg cgccggcgaa tgggttgccc cgaccctgag ccaaatcgga 3060
caggcggacg aagccgcact caaacgcctc gaagcactgg ttcacaaact accgttcaac 3120
gccgaagaga aaaaagccgc agcggccgct ttgggacacg cccgcatccg caccctgcgc 3180
cgtgccgaaa ccgtccttac cggaccgacc ggcgagcgca acagcatctc atggcacgcg 3240
cccaaacgcg tttggataca cggcggcagc acggttcaag cctttgccgc actgaccgaa 3300
cttgccgcct ccggcataca ggcagtggtc gaacccgaca gccccttggc ttcctacact 3360
gccgacttgg aaggtctgct gctggtcaac ggcaaacccg aaaccgccgg catcagccac 3420
gttgccgccc tgtcgccttt ggacagcgcg cgcaaacagg aacttgccgc ccacgacggc 3480
gcactcatcc gcatcctccc ttcggaaaac ggactcgaca tcctgcaagt gtttgaagaa 3540
atctcttgca gcgtcaacac cacagccgcc ggcggcaacg ccagcctgat ggcggtcgcc 3600
gactga 3606
<210> 36
<211> 1201
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0401 protein sequence
<400> 36
Met Phe His Phe Ala Phe Pro Ala Gln Thr Ala Leu Arg Gln Ala Ile
1 5 10 15
Thr Asp Ala Tyr Arg Arg Asn Glu Ile Glu Ala Val Gln Asp Met Leu
20 25 30
Gln Arg Ala Gln Met Ser Asp Glu Glu Arg Asn Ala Ala Ser Glu Leu
35 40 45
Ala Arg Arg Leu Val Thr Gln Val Arg Ala Gly Arg Thr Lys Ala Gly
50 55 60
Gly Val Asp Ala Leu Met His Glu Phe Ser Leu Ser Ser Glu Glu Gly
65 70 75 80
Ile Ala Leu Met Cys Leu Ala Glu Ala Leu Leu Arg Ile Pro Asp Asn
85 90 95
Ala Thr Arg Asp Arg Leu Ile Ala Asp Lys Ile Ser Asp Gly Asn Trp
100 105 110
Lys Ser His Leu Asn Asn Ser Pro Ser Leu Phe Val Asn Ala Ala Ala
115 120 125
Trp Gly Leu Leu Ile Thr Gly Lys Leu Thr Ala Thr Asn Asp Lys Gln
130 135 140
Met Ser Ser Ala Leu Ser Arg Leu Ile Ser Lys Gly Gly Ala Pro Leu
145 150 155 160
Ile Arg Gln Gly Val Asn Tyr Ala Met Arg Leu Leu Gly Lys Gln Phe
165 170 175
Val Thr Gly Gln Thr Ile Glu Glu Ala Leu Gln Asn Gly Lys Glu Arg
180 185 190
Glu Lys Met Gly Tyr Arg Phe Ser Phe Asp Met Leu Gly Glu Ala Ala
195 200 205
Tyr Thr Gln Ala Asp Ala Asp Arg Tyr Tyr Arg Asp Tyr Val Glu Ala
210 215 220
Ile His Ala Ile Gly Lys Asp Ala Ala Gly Gln Gly Val Tyr Glu Gly
225 230 235 240
Asn Gly Ile Ser Val Lys Leu Ser Ala Ile His Pro Arg Tyr Ser Arg
245 250 255
Thr Gln His Gly Arg Val Met Gly Glu Leu Leu Pro Arg Leu Lys Glu
260 265 270
Leu Phe Leu Leu Gly Lys Lys Tyr Asp Ile Gly Ile Asn Ile Asp Ala
275 280 285
Glu Glu Ala Asn Arg Leu Glu Leu Ser Leu Asp Leu Met Glu Ala Leu
290 295 300
Val Ser Asp Pro Asp Leu Ala Gly Tyr Lys Gly Ile Gly Phe Val Val
305 310 315 320
Gln Ala Tyr Gln Lys Arg Cys Pro Phe Val Ile Asp Tyr Leu Ile Asp
325 330 335
Leu Ala Arg Arg Asn Asn Gln Lys Leu Met Ile Arg Leu Val Lys Gly
340 345 350
Ala Tyr Trp Asp Ser Glu Ile Lys Trp Ala Gln Val Asp Gly Leu Asn
355 360 365
Gly Tyr Pro Thr Tyr Thr Arg Lys Val His Thr Asp Ile Ser Tyr Leu
370 375 380
Ala Cys Ala Arg Lys Leu Leu Ser Ala Gln Asp Ala Val Phe Pro Gln
385 390 395 400
Phe Ala Thr His Asn Ala Tyr Thr Leu Gly Ala Ile Tyr Gln Met Gly
405 410 415
Lys Gly Lys Asp Phe Glu His Gln Cys Leu His Gly Met Gly Glu Thr
420 425 430
Leu Tyr Asp Gln Val Val Gly Pro Gln Asn Leu Gly Arg Arg Val Arg
435 440 445
Val Tyr Ala Pro Val Gly Thr His Glu Thr Leu Leu Ala Tyr Leu Val
450 455 460
Arg Arg Leu Leu Glu Asn Gly Ala Asn Ser Ser Phe Val Asn Gln Ile
465 470 475 480
Val Asp Glu Asn Ile Ser Ile Asp Thr Leu Ile Arg Ser Pro Phe Asp
485 490 495
Thr Ile Ala Glu Gln Gly Ile His Leu His Asn Ala Leu Pro Leu Pro
500 505 510
Arg Asp Leu Tyr Gly Lys Cys Arg Leu Asn Ser Gln Gly Val Asp Leu
515 520 525
Ser Asn Glu Asn Val Leu Gln Gln Leu Gln Glu Gln Met Asn Lys Ala
530 535 540
Ala Ala Gln Asp Phe His Ala Ala Ser Ile Val Asn Gly Lys Ala Arg
545 550 555 560
Asp Val Gly Glu Ala Gln Pro Ile Lys Asn Pro Ala Asp His Asp Asp
565 570 575
Ile Val Gly Thr Val Ser Phe Ala Asp Ala Ala Leu Ala Gln Glu Ala
580 585 590
Val Gly Ala Ala Val Ala Ala Phe Pro Glu Trp Ser Ala Thr Pro Ala
595 600 605
Ala Glu Arg Ala Ala Cys Leu Arg Arg Phe Ala Asp Leu Leu Glu Gln
610 615 620
His Thr Pro Ala Leu Met Met Leu Ala Val Arg Glu Ala Gly Lys Thr
625 630 635 640
Leu Asn Asn Ala Ile Ala Glu Val Arg Glu Ala Val Asp Phe Cys Arg
645 650 655
Tyr Tyr Ala Asn Glu Ala Glu His Thr Leu Pro Gln Asp Ala Lys Ala
660 665 670
Val Gly Ala Ile Val Ala Ile Ser Pro Trp Asn Phe Pro Leu Ala Ile
675 680 685
Phe Thr Gly Glu Val Val Ser Ala Leu Ala Ala Gly Asn Thr Val Ile
690 695 700
Ala Lys Pro Ala Glu Gln Thr Ser Leu Ile Ala Gly Tyr Ala Val Ser
705 710 715 720
Leu Met His Glu Ala Gly Ile Pro Thr Ser Ala Leu Gln Leu Val Leu
725 730 735
Gly Ala Gly Asp Val Gly Ala Ala Leu Thr Asn Asp Ala Arg Ile Gly
740 745 750
Gly Val Ile Phe Thr Gly Ser Thr Glu Val Ala Arg Leu Ile Asn Lys
755 760 765
Ala Leu Ala Lys Arg Gly Asp Asn Pro Val Leu Ile Ala Glu Thr Gly
770 775 780
Gly Gln Asn Ala Met Ile Val Asp Ser Thr Ala Leu Ala Glu Gln Val
785 790 795 800
Cys Ala Asp Val Leu Asn Ser Ala Phe Asp Ser Ala Gly Gln Arg Cys
805 810 815
Ser Ala Leu Arg Ile Leu Cys Val Gln Glu Asp Val Ala Asp Arg Met
820 825 830
Leu Asp Met Ile Lys Gly Ala Met Asp Glu Leu Val Val Gly Lys Pro
835 840 845
Ile Gln Leu Thr Thr Asp Val Gly Pro Val Ile Asp Ala Glu Ala Gln
850 855 860
Gln Asn Leu Leu Asn His Ile Asn Lys Met Lys Gly Val Ala Lys Ser
865 870 875 880
Tyr His Glu Val Lys Thr Ala Ala Asp Val Asp Ser Lys Lys Ser Thr
885 890 895
Phe Val Arg Pro Ile Leu Phe Glu Leu Asn Asn Leu Asn Glu Leu Gln
900 905 910
Arg Glu Val Phe Gly Pro Val Leu His Val Val Arg Tyr Arg Ala Asp
915 920 925
Glu Leu Asp Asn Val Ile Asp Gln Ile Asn Ser Lys Gly Tyr Ala Leu
930 935 940
Thr His Gly Val His Ser Arg Ile Glu Gly Thr Val Arg His Ile Arg
945 950 955 960
Ser Arg Ile Glu Ala Gly Asn Val Tyr Val Asn Arg Asn Ile Val Gly
965 970 975
Ala Val Val Gly Val Gln Pro Phe Gly Gly His Gly Leu Ser Gly Thr
980 985 990
Gly Pro Lys Ala Gly Gly Ser Phe Tyr Leu Gln Lys Leu Thr Arg Ala
995 1000 1005
Gly Glu Trp Val Ala Pro Thr Leu Ser Gln Ile Gly Gln Ala Asp Glu
1010 1015 1020
Ala Ala Leu Lys Arg Leu Glu Ala Leu Val His Lys Leu Pro Phe Asn
1025 1030 1035 1040
Ala Glu Glu Lys Lys Ala Ala Ala Ala Ala Leu Gly His Ala Arg Ile
1045 1050 1055
Arg Thr Leu Arg Arg Ala Glu Thr Val Leu Thr Gly Pro Thr Gly Glu
1060 1065 1070
Arg Asn Ser Ile Ser Trp His Ala Pro Lys Arg Val Trp Ile His Gly
1075 1080 1085
Gly Ser Thr Val Gln Ala Phe Ala Ala Leu Thr Glu Leu Ala Ala Ser
1090 1095 1100
Gly Ile Gln Ala Val Val Glu Pro Asp Ser Pro Leu Ala Ser Tyr Thr
1105 1110 1115 1120
Ala Asp Leu Glu Gly Leu Leu Leu Val Asn Gly Lys Pro Glu Thr Ala
1125 1130 1135
Gly Ile Ser His Val Ala Ala Leu Ser Pro Leu Asp Ser Ala Arg Lys
1140 1145 1150
Gln Glu Leu Ala Ala His Asp Gly Ala Leu Ile Arg Ile Leu Pro Ser
1155 1160 1165
Glu Asn Gly Leu Asp Ile Leu Gln Val Phe Glu Glu Ile Ser Cys Ser
1170 1175 1180
Val Asn Thr Thr Ala Ala Gly Gly Asn Ala Ser Leu Met Ala Val Ala
1185 1190 1195 1200
Asp
<210> 37
<211> 1509
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1467 DNA sequence
<400> 37
atgaccacca cccccgcaaa cgtcctcgcc tccgtcgatt tgggttccaa cagtttccgc 60
ctccagattt gcgaaaacaa caacggacaa ttaaaagtca tcgattcgtt caaacagatg 120
gtgcgcttcg ccgccggact ggacgaacag aaaaatctga gtgccgcttc ccaagaacag 180
gctttggact gtctggcaaa attcggcgaa cgcctgcgcg gcttccgccc tgaacaggta 240
cgcgccgtgg caaccaacac attccgcgtt gccaaaaaca tcgcagattt ccttcccaaa 300
gccgaagcgg cattgggttt ccccatcgaa atcatcgccg ggcgcgaaga ggcgcggctg 360
atttataccg gcgtgatcca caccctcccc ccgggcggcg gcaaaatgct ggttatcgac 420
atcggcggcg gttcgacaga atttgtcatc ggctcgacgc tgaatcccga cattaccgaa 480
agcctgccct tgggctgcgt aacctacagc ctgcgcttct tccaaaacaa aatcaccgcc 540
aaagacttcc aatctgccat ttccgccgcc cgcaacgaaa tccagcgtat cagcaaaaat 600
atgaggcgcg aaggttggga tttcgccgtc ggcacatcgg gttcggcaaa atccatccgc 660
gacgtgcttg ccgccgaaat gccccaagag gcggacatta cctacaaagg catgcgcgcc 720
ctcgccgaac gcatcatcga agccggttcg gtcaaaaaag ccaaatttga aaacctgaaa 780
ccggaacgca tcgaagtttt tgccggcgga cttgccgtga tgatggcggc gtttgaggaa 840
atgaaactcg acaggatgac cgtaaccgaa gccgccctgc gcgacggcgt gttttacgat 900
ttgatcgggc gcggtttaaa cgaagatatg cgcggacaaa cggttgccga gttccaacac 960
cgctaccacg tcagcctcaa tcaggcgaaa cgcaccgccg agaccgcgca aacctttatg 1020
gacagcctct gccacgctaa aaacgttaca gttcaagagc ttgccttgtg gcaacagtat 1080
ctcggacgcg ccgccgcgct gcacgaaatc ggtttggaca tcgcccacac cggctatcac 1140
aagcattccg cctacatcct cgaaaacgcc gatatgccgg gtttctcacg caaagaacag 1200
accatacttg cccaactggt catcggtcat cgcggcgata tgaaaaaaat gagcggcatc 1260
atcggcacca acgaaatgtt gtggtatgcc gttttgtccc tgcgccttgc cgcactgttc 1320
tgccgttcgc gccaagacct gtctttcccg aaaaatatgc agttgcgcac ggatacggaa 1380
agctgcggct tcatcctgcg tattgacagg gaatggctgg aacgccatcc cctgattgcc 1440
gacgcattgg aatatgaaag cgtccaatgg caaaaaatca atatgccgtt caaagtcgag 1500
gccgtctga 1509
<210> 38
<211> 323
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1467 protein sequence
<400> 38
Met Thr Thr Thr Ala Asn Val Ala Ser Val Asp Gly Ser Asn Ser Arg
1 5 10 15
Cys Asn Asn Asn Gly Lys Val Asp Ser Lys Met Val Arg Ala Ala Gly
20 25 30
Asp Lys Asn Ser Ala Ala Ser Ala Asp Cys Ala Lys Gly Arg Arg Gly
35 40 45
Arg Val Arg Ala Val Ala Thr Asn Thr Arg Val Ala Lys Asn Ala Asp
50 55 60
Lys Ala Ala Ala Gly Ala Gly Arg Ala Arg Tyr Thr Gly Val His Thr
65 70 75 80
Gly Gly Gly Lys Met Val Asp Gly Gly Gly Ser Thr Val Gly Ser Thr
85 90 95
Asn Asp Thr Ser Gly Cys Val Thr Tyr Ser Arg Asn Lys Thr Ala Lys
100 105 110
Asp Ser Ala Ser Ala Ala Arg Asn Arg Ser Lys Asn Met Arg Arg Gly
115 120 125
Trp Asp Ala Val Gly Thr Ser Gly Ser Ala Lys Ser Arg Asp Val Ala
130 135 140
Ala Met Ala Asp Thr Tyr Lys Gly Met Arg Ala Ala Arg Ala Gly Ser
145 150 155 160
Val Lys Lys Ala Lys Asn Lys Arg Val Ala Gly Gly Ala Val Met Met
165 170 175
Ala Ala Met Lys Asp Arg Met Thr Val Thr Ala Ala Arg Asp Gly Val
180 185 190
Tyr Asp Gly Arg Gly Asn Asp Met Arg Gly Thr Val Ala His Arg Tyr
195 200 205
His Val Ser Asn Ala Lys Arg Thr Ala Thr Ala Thr Met Asp Ser Cys
210 215 220
His Ala Lys Asn Val Thr Val Ala Trp Tyr Gly Arg Ala Ala Ala His
225 230 235 240
Gly Asp Ala His Thr Gly Tyr His Lys His Ser Ala Tyr Asn Ala Asp
245 250 255
Met Gly Ser Arg Lys Thr Ala Val Gly His Arg Gly Asp Met Lys Lys
260 265 270
Met Ser Gly Gly Thr Asn Met Trp Tyr Ala Val Ser Arg Ala Ala Cys
275 280 285
Arg Ser Arg Asp Ser Lys Asn Met Arg Thr Asp Thr Ser Cys Gly Arg
290 295 300
Asp Arg Trp Arg His Ala Asp Ala Tyr Ser Val Trp Lys Asn Met Lys
305 310 315 320
Val Ala Val
<210> 39
<211> 393
<212> DNA
<213> Neisseria meningitidis serogroup B NMB2056 DNA sequence
<400> 39
atgaacggta aatactacta cggcacaggc cgccgcaaaa gttcagtggc tcgtgtattc 60
ctgattaaag gtacaggtca aatcatcgta aacggtcgtc ccgttgacga attcttcgca 120
cgggaaacca gccgaatggt tgttcgccaa cccttggttc tgactgaaaa cgccgaatct 180
ttcgacatca aagtcaatgt tgttggcggc ggcgaaaccg gccagtccgg cgcaatccgc 240
cacggcatta cccgtgccct gatcgacttc gatgccgcgt tgaaacccgc cttgtctcaa 300
gctggttttg ttacccgcga tgcccgcgaa gtcgaacgta aaaaaccggg tctgcgcaaa 360
gcacgccgtg caaaacaatt ctccaaacgt taa 393
<210> 40
<211> 130
<212> PRT
<213> Neisseria meningitidis serogroup B NMB2056 protein sequence
<400> 40
Met Asn Gly Lys Tyr Tyr Tyr Gly Thr Gly Arg Arg Lys Ser Ser Val
1 5 10 15
Ala Arg Val Phe Leu Ile Lys Gly Thr Gly Gln Ile Ile Val Asn Gly
20 25 30
Arg Pro Val Asp Glu Phe Phe Ala Arg Glu Thr Ser Arg Met Val Val
35 40 45
Arg Gln Pro Leu Val Leu Thr Glu Asn Ala Glu Ser Phe Asp Ile Lys
50 55 60
Val Asn Val Val Gly Gly Gly Glu Thr Gly Gln Ser Gly Ala Ile Arg
65 70 75 80
His Gly Ile Thr Arg Ala Leu Ile Asp Phe Asp Ala Ala Leu Lys Pro
85 90 95
Ala Leu Ser Gln Ala Gly Phe Val Thr Arg Asp Ala Arg Glu Val Glu
100 105 110
Arg Lys Lys Pro Gly Leu Arg Lys Ala Arg Arg Ala Lys Gln Phe Ser
115 120 125
Lys Arg
130
<210> 41
<211> 567
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0808 DNA sequence
<400> 41
atgtccgccc tcctccccat catcaaccgc ctgattctgc aaagcccgga cagccgctcg 60
gaacttgccg cctttgcagg caaaacactg accctgaaca ttgccgggct gaaactggcg 120
ggacgcatca cggaagacgg tttgctctcg gcgggaaacg gctttgcaga caccgaaatt 180
accttccgca acagcgcggt acagaaaatc ctccaaggag gcgaacccgg ggcgggcgac 240
atcgggctcg aaggcgacct catcctcggc atcgcggtac tgtccctgct cggcagcctg 300
cgttcccgcg catcggacga attggcacgg attttcggca cgcaggcaga catcggcagc 360
cgtgccgccg acatcggaca cggcatcaaa caaatcggca ggaacatcgc cgaacaaatc 420
ggcggatttt cccgcgaatc cgagtccgca aacatcggca acgaagccct tgccgactgc 480
ctcgacgaaa taagcagact gcgcgacggc gtggaacgcc tcaacgaacg cctcgaccgg 540
ctcgaacgcg acatttggat agactaa 567
<210> 42
<211> 188
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0808 protein sequence
<400> 42
Met Ser Ala Leu Leu Pro Ile Ile Asn Arg Leu Ile Leu Gln Ser Pro
1 5 10 15
Asp Ser Arg Ser Glu Leu Ala Ala Phe Ala Gly Lys Thr Leu Thr Leu
20 25 30
Asn Ile Ala Gly Leu Lys Leu Ala Gly Arg Ile Thr Glu Asp Gly Leu
35 40 45
Leu Ser Ala Gly Asn Gly Phe Ala Asp Thr Glu Ile Thr Phe Arg Asn
50 55 60
Ser Ala Val Gln Lys Ile Leu Gln Gly Gly Glu Pro Gly Ala Gly Asp
65 70 75 80
Ile Gly Leu Glu Gly Asp Leu Ile Leu Gly Ile Ala Val Leu Ser Leu
85 90 95
Leu Gly Ser Leu Arg Ser Arg Ala Ser Asp Glu Leu Ala Arg Ile Phe
100 105 110
Gly Thr Gln Ala Asp Ile Gly Ser Arg Ala Ala Asp Ile Gly His Gly
115 120 125
Ile Lys Gln Ile Gly Arg Asn Ile Ala Glu Gln Ile Gly Gly Phe Ser
130 135 140
Arg Glu Ser Glu Ser Ala Asn Ile Gly Asn Glu Ala Leu Ala Asp Cys
145 150 155 160
Leu Asp Glu Ile Ser Arg Leu Arg Asp Gly Val Glu Arg Leu Asn Glu
165 170 175
Arg Leu Asp Arg Leu Glu Arg Asp Ile Trp Ile Asp
180 185
<210> 43
<211> 627
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0774 DNA sequence
<400> 43
atgaacgtta atgttatcaa ccatccgctc gtccgccaca aattaaccct gatgagggag 60
gcggattgca gcacctacaa attccggacg cttgccaccg agctggcgcg cctgatggca 120
tacgaggcaa gccgtgattt tgaaatcgaa aaatacctta tcgacggatg gtgcggtcag 180
attgaaggcg accgcatcaa gggcaaaaca ttgaccgtcg ttcccatact gcgtgcaggt 240
ttgggtatgc ttgacggtgt gctcgacctg attccgactg ccaaaatcag tgtagtcgga 300
ctgcagcgcg acgaagaaac gctgaagcct atttcctatt ttgagaaatt tgtggacagt 360
atggacgaac gtccggcttt gattatcgat cctatgctgg cgacaggcgg ttcgatggtt 420
gccaccatcg accttttgaa agccaagggc tgcaaaaata tcaaggcact ggtgctggtt 480
gccgcgcccg agggtgtgaa ggcggtcaac gacgcgcacc ctgacgttac gatttacacc 540
gccgcgctcg acagccactt gaacgagaac ggctacatca tccccggctt gggcgatgcg 600
ggcgacaaga ttttcggcac gcgctaa 627
<210> 44
<211> 208
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0774 protein sequence
<400> 44
Met Asn Val Asn Val Ile Asn His Pro Leu Val Arg His Lys Leu Thr
1 5 10 15
Leu Met Arg Glu Ala Asp Cys Ser Thr Tyr Lys Phe Arg Thr Leu Ala
20 25 30
Thr Glu Leu Ala Arg Leu Met Ala Tyr Glu Ala Ser Arg Asp Phe Glu
35 40 45
Ile Glu Lys Tyr Leu Ile Asp Gly Trp Cys Gly Gln Ile Glu Gly Asp
50 55 60
Arg Ile Lys Gly Lys Thr Leu Thr Val Val Pro Ile Leu Arg Ala Gly
65 70 75 80
Leu Gly Met Leu Asp Gly Val Leu Asp Leu Ile Pro Thr Ala Lys Ile
85 90 95
Ser Val Val Gly Leu Gln Arg Asp Glu Glu Thr Leu Lys Pro Ile Ser
100 105 110
Tyr Phe Glu Lys Phe Val Asp Ser Met Asp Glu Arg Pro Ala Leu Ile
115 120 125
Ile Asp Pro Met Leu Ala Thr Gly Gly Ser Met Val Ala Thr Ile Asp
130 135 140
Leu Leu Lys Ala Lys Gly Cys Lys Asn Ile Lys Ala Leu Val Leu Val
145 150 155 160
Ala Ala Pro Glu Gly Val Lys Ala Val Asn Asp Ala His Pro Asp Val
165 170 175
Thr Ile Tyr Thr Ala Ala Leu Asp Ser His Leu Asn Glu Asn Gly Tyr
180 185 190
Ile Ile Pro Gly Leu Gly Asp Ala Gly Asp Lys Ile Phe Gly Thr Arg
195 200 205
<210> 45
<211> 657
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0778 DNA sequence
<400> 45
ttggcgttta ctttaatgcg tcgcgccatg atacgtaaaa tgccctatac ggaagatatg 60
cgcccaggcg ataccgctaa tccttatggt gcgtccaaag cgatggtgga acggatgtta 120
accgacatcc aaaaagccga tccgcgctgg agcatgattt tgttgcgtta tttcaatccg 180
attggcgcgc atgaaagcgg cttgattggc gagcagccaa acggcatccc gaataatttg 240
ttgccttata tctgccaagt ggcggcaggc aaactgccgc aattggcggt atttggcgat 300
gactacccta cccccgacgg cacggggatg cgtgactata ttcatgtgat ggatttggca 360
gaaggccatg tcgcggctat gcaggcaaaa agtaatgtag caggcacgca tttgctgaac 420
ttaggctccg gccgcgcttc ttcggtgttg gaaatcatcc gcgcatttga agcagcttcg 480
ggtttgacga ttccgtatga agtcaaaccg cgccgtgccg gtgatttggc gtgcttctat 540
gccgaccctt cctatacaaa ggcgcaaatc ggctggcaaa cccagcgtga tttaacccaa 600
atgatggaag actcatggcg ctgggtgagt aataatccga atggctacga cgattaa 657
<210> 46
<211> 218
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0778 protein sequence
<400> 46
Met Ala Phe Thr Leu Met Arg Arg Ala Met Ile Arg Lys Met Pro Tyr
1 5 10 15
Thr Glu Asp Met Arg Pro Gly Asp Thr Ala Asn Pro Tyr Gly Ala Ser
20 25 30
Lys Ala Met Val Glu Arg Met Leu Thr Asp Ile Gln Lys Ala Asp Pro
35 40 45
Arg Trp Ser Met Ile Leu Leu Arg Tyr Phe Asn Pro Ile Gly Ala His
50 55 60
Glu Ser Gly Leu Ile Gly Glu Gln Pro Asn Gly Ile Pro Asn Asn Leu
65 70 75 80
Leu Pro Tyr Ile Cys Gln Val Ala Ala Gly Lys Leu Pro Gln Leu Ala
85 90 95
Val Phe Gly Asp Asp Tyr Pro Thr Pro Asp Gly Thr Gly Met Arg Asp
100 105 110
Tyr Ile His Val Met Asp Leu Ala Glu Gly His Val Ala Ala Met Gln
115 120 125
Ala Lys Ser Asn Val Ala Gly Thr His Leu Leu Asn Leu Gly Ser Gly
130 135 140
Arg Ala Ser Ser Val Leu Glu Ile Ile Arg Ala Phe Glu Ala Ala Ser
145 150 155 160
Gly Leu Thr Ile Pro Tyr Glu Val Lys Pro Arg Arg Ala Gly Asp Leu
165 170 175
Ala Cys Phe Tyr Ala Asp Pro Ser Tyr Thr Lys Ala Gln Ile Gly Trp
180 185 190
Gln Thr Gln Arg Asp Leu Thr Gln Met Met Glu Asp Ser Trp Arg Trp
195 200 205
Val Ser Asn Asn Pro Asn Gly Tyr Asp Asp
210 215
<210> 47
<211> 999
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0337 DNA sequence
<400> 47
atgagcagac ccgtacccgc cgtattcggc agcgtttttc acagtcaaat gcccgtcctc 60
gcctaccgcg aaggcaaatg gcagccgacc gaatggcaat cttcccaaga cctctccctc 120
gcaccgggcg cgcacgccct gcactacggc agcgaatgtt tcgagggact gaaagccttc 180
cgtcaggcag acggcaaaat cgtgctgttc cgtccgactg ccaatatcgc gcgtatgcgg 240
caaagtgcgg acattttgca cctgccgcgc cccgaaaccg aagcttatct tgacgcgcta 300
atcaaattgg tcaaacgtgc cgccgatgaa attcccgatg cgcctgccgc cctgtacctg 360
cgtccgacct taatcggtac cgatcccgtt atcggcaagg ccggttctcc ttccgaaacc 420
gccctgctgt atattttggc ttcccccgtc ggcgactatt tcaaagtcgg atcgcccgtc 480
aaaattttgg tggaaaccga acacatccgc tgcgccccgc atatgggccg cgtcaaatgc 540
ggcggcaact acgcttccgc catgcactgg gtgctgaagg cgaaagccga atatggcgca 600
aatcaagtcc tgttctgccc gaacggcgac gtgcaggaaa ccggcgcgtc caactttatc 660
ctgattaacg gcgatgaaat cattaccaaa ccgctgaccg acgagttttt gcacggcgta 720
acccgcgatt ccgtactgac ggttgccaaa gatttgggct ataccgtcag cgaacgcaat 780
ttcacggttg acgaactcaa agctgcggtg gaaaacggtg cggaagccat tttgaccggt 840
acggcagccg tcatctcgcc cgttacttcc ttcgtcatcg gcggcaaaga aatcgaagtg 900
aaaagccaag aacgcggcta tgccatccgt aaggcgatta ccgacatcca gtatggtttg 960
gcggaagaca aatacggctg gctggttgaa gtgtgctga 999
<210> 48
<211> 332
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0337 protein sequence
<400> 48
Met Ser Arg Pro Val Pro Ala Val Phe Gly Ser Val Phe His Ser Gln
1 5 10 15
Met Pro Val Leu Ala Tyr Arg Glu Gly Lys Trp Gln Pro Thr Glu Trp
20 25 30
Gln Ser Ser Gln Asp Leu Ser Leu Ala Pro Gly Ala His Ala Leu His
35 40 45
Tyr Gly Ser Glu Cys Phe Glu Gly Leu Lys Ala Phe Arg Gln Ala Asp
50 55 60
Gly Lys Ile Val Leu Phe Arg Pro Thr Ala Asn Ile Ala Arg Met Arg
65 70 75 80
Gln Ser Ala Asp Ile Leu His Leu Pro Arg Pro Glu Thr Glu Ala Tyr
85 90 95
Leu Asp Ala Leu Ile Lys Leu Val Lys Arg Ala Ala Asp Glu Ile Pro
100 105 110
Asp Ala Pro Ala Ala Leu Tyr Leu Arg Pro Thr Leu Ile Gly Thr Asp
115 120 125
Pro Val Ile Gly Lys Ala Gly Ser Pro Ser Glu Thr Ala Leu Leu Tyr
130 135 140
Ile Leu Ala Ser Pro Val Gly Asp Tyr Phe Lys Val Gly Ser Pro Val
145 150 155 160
Lys Ile Leu Val Glu Thr Glu His Ile Arg Cys Ala Pro His Met Gly
165 170 175
Arg Val Lys Cys Gly Gly Asn Tyr Ala Ser Ala Met His Trp Val Leu
180 185 190
Lys Ala Lys Ala Glu Tyr Gly Ala Asn Gln Val Leu Phe Cys Pro Asn
195 200 205
Gly Asp Val Gln Glu Thr Gly Ala Ser Asn Phe Ile Leu Ile Asn Gly
210 215 220
Asp Glu Ile Ile Thr Lys Pro Leu Thr Asp Glu Phe Leu His Gly Val
225 230 235 240
Thr Arg Asp Ser Val Leu Thr Val Ala Lys Asp Leu Gly Tyr Thr Val
245 250 255
Ser Glu Arg Asn Phe Thr Val Asp Glu Leu Lys Ala Ala Val Glu Asn
260 265 270
Gly Ala Glu Ala Ile Leu Thr Gly Thr Ala Ala Val Ile Ser Pro Val
275 280 285
Thr Ser Phe Val Ile Gly Gly Lys Glu Ile Glu Val Lys Ser Gln Glu
290 295 300
Arg Gly Tyr Ala Ile Arg Lys Ala Ile Thr Asp Ile Gln Tyr Gly Leu
305 310 315 320
Ala Glu Asp Lys Tyr Gly Trp Leu Val Glu Val Cys
325 330
<210> 49
<211> 774
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0191 DNA sequence
<400> 49
atgagtgcga acatccttgc catcgccaat cagaagggcg gtgtgggcaa aacgacgacg 60
acggtaaatt tggcggcttc gctggcatcg cgcggcaaac gcgtgctggt ggtcgatttg 120
gatccgcagg gcaatgcgac gacgggcagc ggcatcgaca aggcgggttt gcagtccggc 180
gtttatcagg tcttattggg cgatgcggac gtgcagtcgg cggcggtacg cagcaaagag 240
ggcggatacg ctgtgttggg tgcgaaccgc gcgctggccg gcgcggaaat cgaactggtg 300
caggaaatcg cccgggaagt gcgtttgaaa aacgcgctca aggcagtgga agaagattac 360
gactttatcc tgatcgactg cccgccttcg ctgacgctgt tgacgcttaa cgggctggtg 420
gcggcgggcg gcgtgattgt gccgatgttg tgcgaatatt acgcgctgga agggatttcc 480
gatttgattg cgaccgtgcg caaaatccgt caggcggtca atcccgattt ggacatcacg 540
ggcatcgtgc gcacgatgta cgacagccgc agcaggctgg ttgccgaagt cagcgaacag 600
ttgcgcagcc atttcgggga tttgcttttt gaaaccgtca tcccgcgcaa tatccgcctt 660
gcggaagcgc cgagccacgg tatgccggtg atggcttacg acgcgcaggc aaagggtacc 720
aaggcgtatc ttgccttggc ggacgagctg gcggcgaggg tgtcggggaa atag 774
<210> 50
<211> 257
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0191 protein sequence
<400> 50
Met Ser Ala Asn Ile Leu Ala Ile Ala Asn Gln Lys Gly Gly Val Gly
1 5 10 15
Lys Thr Thr Thr Thr Val Asn Leu Ala Ala Ser Leu Ala Ser Arg Gly
20 25 30
Lys Arg Val Leu Val Val Asp Leu Asp Pro Gln Gly Asn Ala Thr Thr
35 40 45
Gly Ser Gly Ile Asp Lys Ala Gly Leu Gln Ser Gly Val Tyr Gln Val
50 55 60
Leu Leu Gly Asp Ala Asp Val Gln Ser Ala Ala Val Arg Ser Lys Glu
65 70 75 80
Gly Gly Tyr Ala Val Leu Gly Ala Asn Arg Ala Leu Ala Gly Ala Glu
85 90 95
Ile Glu Leu Val Gln Glu Ile Ala Arg Glu Val Arg Leu Lys Asn Ala
100 105 110
Leu Lys Ala Val Glu Glu Asp Tyr Asp Phe Ile Leu Ile Asp Cys Pro
115 120 125
Pro Ser Leu Thr Leu Leu Thr Leu Asn Gly Leu Val Ala Ala Gly Gly
130 135 140
Val Ile Val Pro Met Leu Cys Glu Tyr Tyr Ala Leu Glu Gly Ile Ser
145 150 155 160
Asp Leu Ile Ala Thr Val Arg Lys Ile Arg Gln Ala Val Asn Pro Asp
165 170 175
Leu Asp Ile Thr Gly Ile Val Arg Thr Met Tyr Asp Ser Arg Ser Arg
180 185 190
Leu Val Ala Glu Val Ser Glu Gln Leu Arg Ser His Phe Gly Asp Leu
195 200 205
Leu Phe Glu Thr Val Ile Pro Arg Asn Ile Arg Leu Ala Glu Ala Pro
210 215 220
Ser His Gly Met Pro Val Met Ala Tyr Asp Ala Gln Ala Lys Gly Thr
225 230 235 240
Lys Ala Tyr Leu Ala Leu Ala Asp Glu Leu Ala Ala Arg Val Ser Gly
245 250 255
Lys
<210> 51
<211> 1335
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1710 DNA sequence
<400> 51
atgactgacc tgaacaccct gtttgccaac ctcaaacaac gcaatcccaa tcaggagccg 60
ttccatcagg cggttgaaga agtcttcatg agtctcgatc cgtttttggc aaaaaatccg 120
aaatacaccc agcaaagcct gctggaacgc atcgtcgaac ccgaacgcgt cgtgatgttc 180
cgcgtaacct ggcaggacga taaagggcaa gtccaagtca accggggcta ccgcgtgcaa 240
atgagttccg ccatcggtcc ttacaaaggc ggcctgcgct tccatccgac cgtcgatttg 300
ggcgtattga aattcctcgc ttttgaacaa gtgttcaaaa acgccttgac caccctgcct 360
atgggcggcg gcaaaggcgg ttccgacttc gaccccaaag gcaaatccga tgccgaagta 420
atgcgcttct gccaagcctt tatgaccgaa ctctaccgcc acatcggcgc ggacaccgat 480
gttccggccg gcgacatcgg cgtaggcggg cgcgaaatcg gctacctgtt cggacaatac 540
aaaaaaatcc gcaacgagtt ttcttccgtc ctgaccggca aaggtttgga atggggcggc 600
agcctcatcc gtcccgaagc gaccggctac ggctgcgtct atttcgccca agcgatgctg 660
caaacccgca acgatagttt tgaaggcaaa cgcgtcctga tttccggctc cggcaatgtg 720
gcgcaatacg ccgccgaaaa agccatccaa ctgggtgcga aagtactgac cgtttccgac 780
tccaacggct tcgtcctctt ccccgacagc ggtatgaccg aagcgcaact cgccgccttg 840
atcgaattga aagaagtccg ccgcgaacgc gttgccacct acgccaaaga gcaaggtctg 900
caatactttg aaaaacaaaa accgtggggc gtcgccgccg aaatcgccct gccctgcgcg 960
acccagaacg aattggacga agaagccgcc aaaaccctgt tggcaaacgg ctgctacgtc 1020
gttgccgaag gtgcgaatat gccgtcgact ttgggcgcgg tcgagcaatt tatcaaagcc 1080
ggcatcctct acgccccggg aaaagcctcc aatgccggcg gcgtggcaac ttcaggtttg 1140
gaaatgagcc aaaacgccat ccgcctgtct tggactcgtg aagaagtcga ccaacgcctg 1200
ttcggcatca tgcaaagcat ccacgaatcc tgtctgaaat acggcaaagt cggcgacaca 1260
gtaaactacg tcaatggtgc gaacattgcc ggtttcgtca aagttgccga tgcgatgctg 1320
gcgcaaggct tctaa 1335
<210> 52
<211> 444
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1710 protein sequence
<400> 52
Met Thr Asp Leu Asn Thr Leu Phe Ala Asn Leu Lys Gln Arg Asn Pro
1 5 10 15
Asn Gln Glu Pro Phe His Gln Ala Val Glu Glu Val Phe Met Ser Leu
20 25 30
Asp Pro Phe Leu Ala Lys Asn Pro Lys Tyr Thr Gln Gln Ser Leu Leu
35 40 45
Glu Arg Ile Val Glu Pro Glu Arg Val Val Met Phe Arg Val Thr Trp
50 55 60
Gln Asp Asp Lys Gly Gln Val Gln Val Asn Arg Gly Tyr Arg Val Gln
65 70 75 80
Met Ser Ser Ala Ile Gly Pro Tyr Lys Gly Gly Leu Arg Phe His Pro
85 90 95
Thr Val Asp Leu Gly Val Leu Lys Phe Leu Ala Phe Glu Gln Val Phe
100 105 110
Lys Asn Ala Leu Thr Thr Leu Pro Met Gly Gly Gly Lys Gly Gly Ser
115 120 125
Asp Phe Asp Pro Lys Gly Lys Ser Asp Ala Glu Val Met Arg Phe Cys
130 135 140
Gln Ala Phe Met Thr Glu Leu Tyr Arg His Ile Gly Ala Asp Thr Asp
145 150 155 160
Val Pro Ala Gly Asp Ile Gly Val Gly Gly Arg Glu Ile Gly Tyr Leu
165 170 175
Phe Gly Gln Tyr Lys Lys Ile Arg Asn Glu Phe Ser Ser Val Leu Thr
180 185 190
Gly Lys Gly Leu Glu Trp Gly Gly Ser Leu Ile Arg Pro Glu Ala Thr
195 200 205
Gly Tyr Gly Cys Val Tyr Phe Ala Gln Ala Met Leu Gln Thr Arg Asn
210 215 220
Asp Ser Phe Glu Gly Lys Arg Val Leu Ile Ser Gly Ser Gly Asn Val
225 230 235 240
Ala Gln Tyr Ala Ala Glu Lys Ala Ile Gln Leu Gly Ala Lys Val Leu
245 250 255
Thr Val Ser Asp Ser Asn Gly Phe Val Leu Phe Pro Asp Ser Gly Met
260 265 270
Thr Glu Ala Gln Leu Ala Ala Leu Ile Glu Leu Lys Glu Val Arg Arg
275 280 285
Glu Arg Val Ala Thr Tyr Ala Lys Glu Gln Gly Leu Gln Tyr Phe Glu
290 295 300
Lys Gln Lys Pro Trp Gly Val Ala Ala Glu Ile Ala Leu Pro Cys Ala
305 310 315 320
Thr Gln Asn Glu Leu Asp Glu Glu Ala Ala Lys Thr Leu Leu Ala Asn
325 330 335
Gly Cys Tyr Val Val Ala Glu Gly Ala Asn Met Pro Ser Thr Leu Gly
340 345 350
Ala Val Glu Gln Phe Ile Lys Ala Gly Ile Leu Tyr Ala Pro Gly Lys
355 360 365
Ala Ser Asn Ala Gly Gly Val Ala Thr Ser Gly Leu Glu Met Ser Gln
370 375 380
Asn Ala Ile Arg Leu Ser Trp Thr Arg Glu Glu Val Asp Gln Arg Leu
385 390 395 400
Phe Gly Ile Met Gln Ser Ile His Glu Ser Cys Leu Lys Tyr Gly Lys
405 410 415
Val Gly Asp Thr Val Asn Tyr Val Asn Gly Ala Asn Ile Ala Gly Phe
420 425 430
Val Lys Val Ala Asp Ala Met Leu Ala Gln Gly Phe
435 440
<210> 53
<211> 867
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0062 DNA sequence
<400> 53
Ala Thr Gly Ala Ala Ala Gly Gly Cys Ala Thr Cys Ala Thr Ala Cys
1 5 10 15
Thr Gly Gly Cys Ala Gly Gly Cys Gly Gly Cys Ala Gly Cys Gly Gly
20 25 30
Cys Ala Cys Gly Cys Gly Cys Cys Thr Cys Thr Ala Cys Cys Cys Cys
35 40 45
Ala Thr Cys Ala Cys Gly Cys Gly Cys Gly Gly Cys Gly Thr Ala Thr
50 55 60
Cys Cys Ala Ala Ala Cys Ala Gly Cys Thr Cys Cys Thr Gly Cys Cys
65 70 75 80
Cys Gly Thr Gly Thr Ala Cys Gly Ala Cys Ala Ala Ala Cys Cys Gly
85 90 95
Ala Thr Gly Ala Thr Thr Thr Ala Thr Thr Ala Cys Cys Cys Cys Thr
100 105 110
Thr Gly Thr Cys Gly Gly Thr Thr Thr Thr Gly Ala Thr Gly Cys Thr
115 120 125
Gly Gly Cys Gly Gly Gly Ala Ala Thr Cys Cys Gly Cys Gly Ala Thr
130 135 140
Ala Thr Thr Thr Thr Gly Gly Thr Gly Ala Thr Thr Ala Cys Cys Gly
145 150 155 160
Cys Gly Cys Cys Thr Gly Ala Ala Gly Ala Cys Ala Ala Cys Gly Cys
165 170 175
Cys Thr Cys Thr Thr Thr Cys Ala Ala Ala Cys Gly Cys Cys Thr Gly
180 185 190
Cys Thr Thr Gly Gly Cys Gly Ala Cys Gly Gly Cys Ala Gly Cys Gly
195 200 205
Ala Thr Thr Thr Cys Gly Gly Cys Ala Thr Thr Thr Cys Cys Ala Thr
210 215 220
Cys Ala Gly Thr Thr Ala Thr Gly Cys Cys Gly Thr Gly Cys Ala Ala
225 230 235 240
Cys Cys Cys Ala Gly Thr Cys Cys Gly Gly Ala Cys Gly Gly Cys Thr
245 250 255
Thr Gly Gly Cys Ala Cys Ala Gly Gly Cys Ala Thr Thr Thr Ala Thr
260 265 270
Cys Ala Thr Cys Gly Gly Cys Gly Ala Ala Gly Ala Ala Thr Thr Thr
275 280 285
Ala Thr Cys Gly Gly Cys Ala Ala Cys Gly Ala Cys Ala Ala Thr Gly
290 295 300
Thr Thr Thr Gly Cys Thr Thr Gly Gly Thr Thr Thr Thr Gly Gly Gly
305 310 315 320
Cys Gly Ala Cys Ala Ala Thr Ala Thr Thr Thr Thr Thr Thr Ala Cys
325 330 335
Gly Gly Thr Cys Ala Gly Thr Cys Gly Thr Thr Thr Ala Cys Gly Cys
340 345 350
Ala Ala Ala Cys Ala Thr Thr Gly Ala Ala Ala Cys Ala Gly Gly Cys
355 360 365
Gly Gly Cys Ala Gly Cys Gly Cys Ala Ala Ala Cys Gly Cys Ala Cys
370 375 380
Gly Gly Cys Gly Cys Ala Ala Cys Cys Gly Thr Gly Thr Thr Thr Gly
385 390 395 400
Cys Thr Thr Ala Thr Cys Ala Gly Gly Thr Cys Ala Ala Ala Ala Ala
405 410 415
Cys Cys Cys Cys Gly Ala Ala Cys Gly Thr Thr Thr Cys Gly Gly Cys
420 425 430
Gly Thr Gly Gly Thr Thr Gly Ala Ala Thr Thr Thr Ala Ala Cys Gly
435 440 445
Ala Ala Ala Ala Cys Thr Thr Cys Cys Gly Cys Gly Cys Cys Gly Thr
450 455 460
Thr Thr Cys Cys Ala Thr Cys Gly Ala Ala Gly Ala Ala Ala Ala Ala
465 470 475 480
Cys Cys Gly Cys Ala Ala Cys Gly Gly Cys Cys Cys Ala Ala Ala Thr
485 490 495
Cys Cys Gly Ala Thr Thr Gly Gly Gly Cys Gly Gly Thr Ala Ala Cys
500 505 510
Cys Gly Gly Cys Thr Thr Gly Thr Ala Thr Thr Thr Cys Thr Ala Cys
515 520 525
Gly Ala Cys Ala Ala Cys Cys Gly Cys Gly Cys Cys Gly Thr Cys Gly
530 535 540
Ala Gly Thr Thr Cys Gly Cys Cys Ala Ala Ala Cys Ala Gly Cys Thr
545 550 555 560
Cys Ala Ala Ala Cys Cys Gly Thr Cys Cys Gly Cys Ala Cys Gly Cys
565 570 575
Gly Gly Cys Gly Ala Ala Thr Thr Gly Gly Ala Ala Ala Thr Thr Ala
580 585 590
Cys Cys Gly Ala Cys Cys Thr Cys Ala Ala Cys Cys Gly Gly Ala Thr
595 600 605
Gly Thr Ala Thr Thr Thr Gly Gly Ala Ala Gly Ala Cys Gly Gly Cys
610 615 620
Thr Cys Gly Cys Thr Cys Thr Cys Cys Gly Thr Thr Cys Ala Ala Ala
625 630 635 640
Thr Ala Thr Thr Gly Gly Gly Ala Cys Gly Cys Gly Gly Thr Thr Thr
645 650 655
Cys Gly Cys Gly Thr Gly Gly Cys Thr Gly Gly Ala Cys Ala Cys Cys
660 665 670
Gly Gly Cys Ala Cys Cys Cys Ala Cys Gly Ala Gly Ala Gly Cys Cys
675 680 685
Thr Gly Cys Ala Cys Gly Ala Ala Gly Cys Cys Gly Cys Thr Thr Cys
690 695 700
Ala Thr Thr Cys Gly Thr Cys Cys Ala Ala Ala Cys Cys Gly Thr Gly
705 710 715 720
Cys Ala Ala Ala Ala Thr Ala Thr Cys Cys Ala Ala Ala Ala Cys Cys
725 730 735
Thr Gly Cys Ala Cys Ala Thr Cys Gly Cys Cys Thr Gly Cys Cys Thr
740 745 750
Cys Gly Ala Ala Gly Ala Ala Ala Thr Cys Gly Cys Thr Thr Gly Gly
755 760 765
Cys Gly Cys Ala Ala Cys Gly Gly Thr Thr Gly Gly Cys Thr Thr Thr
770 775 780
Cys Cys Gly Ala Thr Gly Ala Ala Ala Ala Ala Cys Thr Gly Gly Ala
785 790 795 800
Ala Gly Ala Ala Thr Thr Gly Gly Cys Gly Cys Gly Cys Cys Cys Gly
805 810 815
Ala Thr Gly Gly Cys Gly Ala Ala Ala Ala Ala Cys Cys Ala Ala Thr
820 825 830
Ala Cys Gly Gly Cys Cys Ala Ala Thr Ala Thr Thr Thr Gly Cys Thr
835 840 845
Gly Cys Gly Cys Cys Thr Gly Thr Thr Gly Ala Ala Ala Ala Ala Ala
850 855 860
Thr Ala Ala
865
<210> 54
<211> 288
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0062 protein sequence
<400> 54
Met Lys Gly Ile Ile Leu Ala Gly Gly Ser Gly Thr Arg Leu Tyr Pro
1 5 10 15
Ile Thr Arg Gly Val Ser Lys Gln Leu Leu Pro Val Tyr Asp Lys Pro
20 25 30
Met Ile Tyr Tyr Pro Leu Ser Val Leu Met Leu Ala Gly Ile Arg Asp
35 40 45
Ile Leu Val Ile Thr Ala Pro Glu Asp Asn Ala Ser Phe Lys Arg Leu
50 55 60
Leu Gly Asp Gly Ser Asp Phe Gly Ile Ser Ile Ser Tyr Ala Val Gln
65 70 75 80
Pro Ser Pro Asp Gly Leu Ala Gln Ala Phe Ile Ile Gly Glu Glu Phe
85 90 95
Ile Gly Asn Asp Asn Val Cys Leu Val Leu Gly Asp Asn Ile Phe Tyr
100 105 110
Gly Gln Ser Phe Thr Gln Thr Leu Lys Gln Ala Ala Ala Gln Thr His
115 120 125
Gly Ala Thr Val Phe Ala Tyr Gln Val Lys Asn Pro Glu Arg Phe Gly
130 135 140
Val Val Glu Phe Asn Glu Asn Phe Arg Ala Val Ser Ile Glu Glu Lys
145 150 155 160
Pro Gln Arg Pro Lys Ser Asp Trp Ala Val Thr Gly Leu Tyr Phe Tyr
165 170 175
Asp Asn Arg Ala Val Glu Phe Ala Lys Gln Leu Lys Pro Ser Ala Arg
180 185 190
Gly Glu Leu Glu Ile Thr Asp Leu Asn Arg Met Tyr Leu Glu Asp Gly
195 200 205
Ser Leu Ser Val Gln Ile Leu Gly Arg Gly Phe Ala Trp Leu Asp Thr
210 215 220
Gly Thr His Glu Ser Leu His Glu Ala Ala Ser Phe Val Gln Thr Val
225 230 235 240
Gln Asn Ile Gln Asn Leu His Ile Ala Cys Leu Glu Glu Ile Ala Trp
245 250 255
Arg Asn Gly Trp Leu Ser Asp Glu Lys Leu Glu Glu Leu Ala Arg Pro
260 265 270
Met Ala Lys Asn Gln Tyr Gly Gln Tyr Leu Leu Arg Leu Leu Lys Lys
275 280 285
<210> 55
<211> 1791
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1333 DNA sequence
<400> 55
atgcgctaca aaccccttct gcttgccctg atgctcgttt tttccacgcc cgccgttgcc 60
gcccacgacg cggcacacaa ccgttccgcc gaagtgaaaa aacagacgaa gaacaaaaaa 120
gaacagcccg aagcggcgga aggcaaaaaa gaaaaaggca aaaatggcgc agtgaaagat 180
aaaaaaacag gcggcaaaga ggcggcaaaa gagggcaaag agtccaaaaa aaccgccaaa 240
aaccgcaaag aagcagagaa ggaggcgaca tccaggcagt ctgcgcgcaa aggacgcgaa 300
ggggataaga aatcgaaggc ggaacacaaa aaggcacatg gcaagcccgt gtccggatcc 360
aaagaaaaaa acgcaaaaac acagcctgaa aacaaacaag gcaaaaaaga ggcaaaagga 420
cagggcaatc cgcgcaaggg cggcaaggcg gaaaaagaca ctgtttctgc aaataaaaaa 480
gtccgttccg acaagaacgg caaagcagtg aaacaggaca aaaaatacag ggaagagaaa 540
aatgccaaaa ccgattccga cgaattgaaa gccgccgttg ccgctgccac caatgatgtc 600
gaaaacaaaa aagccctgct caaacaaagc gaaggaatgc tgcttcatgt cagcaattcc 660
ctcaaacagc ttcaggaaga gcgtatccgc caagagcgta tccgtcaggc gcgcggcaac 720
cttgcttccg tcaaccgcaa acagcgcgag gcttgggaca agttccaaaa actcaatacc 780
gagctgaacc gtttgaaaac ggaagtcgcc gctacgaaag cgcagatttc ccgtttcgta 840
tcggggaact ataaaaacag ccagccgaat gcggttgccc tgttcctgaa aaacgccgaa 900
ccgggtcaga aaaaccgctt tttgcgttat acgcgttatg taaacgcctc caatcgggaa 960
gttgtcaagg atttggaaaa acagcagaag gctttggcgg tacaagagca gaaaatcaac 1020
aatgagcttg cccgtttgaa gaaaattcag gcaaacgtgc aatctctgct gaaaaaacag 1080
ggtgtaaccg atgcggcgga acagacggaa agccgcagac agaatgccaa aatcgccaaa 1140
gatgcccgaa aactgctgga acagaaaggg aacgagcagc agctgaacaa gctcttgagc 1200
aatttggaga agaaaaaggc cgaacaccgc attcaggatg cggaagcaaa aagaaaattg 1260
gctgaagcca gactggcggc agccgaaaaa gccagaaaag aagcggcgca gcagaaggct 1320
gaagcacgac gtgcggaaat gtccaacctg accgccgaag acaggaacat ccaagcgcct 1380
tcggttatgg gtatcggcag tgccgacggt ttcagccgca tgcaaggacg tttgaaaaaa 1440
ccggttgacg gtgtgccgac cggacttttc gggcagaacc ggagcggcgg cgatatttgg 1500
aaaggcgtgt tctattccac tgcaccggca acggttgaaa gcattgcgcc gggaacggta 1560
agctatgcgg acgagttgga cggctacggc aaagtggtcg tggtcgatca cggcgagaac 1620
tacatcagca tctatgccgg tttgagcgaa atttccgtcg gcaagggtta tatggtcgcg 1680
gcaggaagca aaatcggctc gagcgggtcg ctgccggacg gggaagaggg gctttacctg 1740
caaatacgtt atcaaggtca ggtattgaac ccttcgagct ggatacgttg a 1791
<210> 56
<211> 596
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1333 protein sequence
<400> 56
Met Arg Tyr Lys Pro Leu Leu Leu Ala Leu Met Leu Val Phe Ser Thr
1 5 10 15
Pro Ala Val Ala Ala His Asp Ala Ala His Asn Arg Ser Ala Glu Val
20 25 30
Lys Lys Gln Thr Lys Asn Lys Lys Glu Gln Pro Glu Ala Ala Glu Gly
35 40 45
Lys Lys Glu Lys Gly Lys Asn Gly Ala Val Lys Asp Lys Lys Thr Gly
50 55 60
Gly Lys Glu Ala Ala Lys Glu Gly Lys Glu Ser Lys Lys Thr Ala Lys
65 70 75 80
Asn Arg Lys Glu Ala Glu Lys Glu Ala Thr Ser Arg Gln Ser Ala Arg
85 90 95
Lys Gly Arg Glu Gly Asp Lys Lys Ser Lys Ala Glu His Lys Lys Ala
100 105 110
His Gly Lys Pro Val Ser Gly Ser Lys Glu Lys Asn Ala Lys Thr Gln
115 120 125
Pro Glu Asn Lys Gln Gly Lys Lys Glu Ala Lys Gly Gln Gly Asn Pro
130 135 140
Arg Lys Gly Gly Lys Ala Glu Lys Asp Thr Val Ser Ala Asn Lys Lys
145 150 155 160
Val Arg Ser Asp Lys Asn Gly Lys Ala Val Lys Gln Asp Lys Lys Tyr
165 170 175
Arg Glu Glu Lys Asn Ala Lys Thr Asp Ser Asp Glu Leu Lys Ala Ala
180 185 190
Val Ala Ala Ala Thr Asn Asp Val Glu Asn Lys Lys Ala Leu Leu Lys
195 200 205
Gln Ser Glu Gly Met Leu Leu His Val Ser Asn Ser Leu Lys Gln Leu
210 215 220
Gln Glu Glu Arg Ile Arg Gln Glu Arg Ile Arg Gln Ala Arg Gly Asn
225 230 235 240
Leu Ala Ser Val Asn Arg Lys Gln Arg Glu Ala Trp Asp Lys Phe Gln
245 250 255
Lys Leu Asn Thr Glu Leu Asn Arg Leu Lys Thr Glu Val Ala Ala Thr
260 265 270
Lys Ala Gln Ile Ser Arg Phe Val Ser Gly Asn Tyr Lys Asn Ser Gln
275 280 285
Pro Asn Ala Val Ala Leu Phe Leu Lys Asn Ala Glu Pro Gly Gln Lys
290 295 300
Asn Arg Phe Leu Arg Tyr Thr Arg Tyr Val Asn Ala Ser Asn Arg Glu
305 310 315 320
Val Val Lys Asp Leu Glu Lys Gln Gln Lys Ala Leu Ala Val Gln Glu
325 330 335
Gln Lys Ile Asn Asn Glu Leu Ala Arg Leu Lys Lys Ile Gln Ala Asn
340 345 350
Val Gln Ser Leu Leu Lys Lys Gln Gly Val Thr Asp Ala Ala Glu Gln
355 360 365
Thr Glu Ser Arg Arg Gln Asn Ala Lys Ile Ala Lys Asp Ala Arg Lys
370 375 380
Leu Leu Glu Gln Lys Gly Asn Glu Gln Gln Leu Asn Lys Leu Leu Ser
385 390 395 400
Asn Leu Glu Lys Lys Lys Ala Glu His Arg Ile Gln Asp Ala Glu Ala
405 410 415
Lys Arg Lys Leu Ala Glu Ala Arg Leu Ala Ala Ala Glu Lys Ala Arg
420 425 430
Lys Glu Ala Ala Gln Gln Lys Ala Glu Ala Arg Arg Ala Glu Met Ser
435 440 445
Asn Leu Thr Ala Glu Asp Arg Asn Ile Gln Ala Pro Ser Val Met Gly
450 455 460
Ile Gly Ser Ala Asp Gly Phe Ser Arg Met Gln Gly Arg Leu Lys Lys
465 470 475 480
Pro Val Asp Gly Val Pro Thr Gly Leu Phe Gly Gln Asn Arg Ser Gly
485 490 495
Gly Asp Ile Trp Lys Gly Val Phe Tyr Ser Thr Ala Pro Ala Thr Val
500 505 510
Glu Ser Ile Ala Pro Gly Thr Val Ser Tyr Ala Asp Glu Leu Asp Gly
515 520 525
Tyr Gly Lys Val Val Val Val Asp His Gly Glu Asn Tyr Ile Ser Ile
530 535 540
Tyr Ala Gly Leu Ser Glu Ile Ser Val Gly Lys Gly Tyr Met Val Ala
545 550 555 560
Ala Gly Ser Lys Ile Gly Ser Ser Gly Ser Leu Pro Asp Gly Glu Glu
565 570 575
Gly Leu Tyr Leu Gln Ile Arg Tyr Gln Gly Gln Val Leu Asn Pro Ser
580 585 590
Ser Trp Ile Arg
595
<210> 57
<211> 1131
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0377 DNA sequence
<400> 57
atggcgtttt gcaccagttt gggagtgatg atggaaacac agctttacat cggcatcatg 60
tcgggaacca gcatggacgg ggcggatgcc gtactgatac ggatggacgg cggcaaatgg 120
ctgggcgcgg aagggcacgc ctttaccccc taccccggca ggttacgccg ccaattgctg 180
gatttgcagg acacaggcgc agacgaactg caccgcagca ggattttgtc gcaagaactc 240
agccgcctat atgcgcaaac cgccgccgaa ctgctgtgca gtcaaaacct cgcaccgtcc 300
gacattaccg ccctcggctg ccacgggcaa accgtccgac acgcgccgga acacggttac 360
agcatacagc ttgccgattt gccgctgctg gcggaacgga cgcggatttt taccgtcggc 420
gacttccgca gccgcgacct tgcggccggc ggacaaggcg cgccactcgt ccccgccttt 480
cacgaagccc tgttccgcga caacagggaa acacgcgcgg tactgaacat cggcgggatt 540
gccaacatca gcgtactccc ccccgacgca cccgccttcg gcttcgacac agggccgggc 600
aatatgctga tggacgcgtg gacgcaggca cactggcagc ttccttacga caaaaacggt 660
gcaaaggcgg cacaaggcaa catattgccg caactgctcg acaggctgct cgcccacccg 720
tatttcgcac aaccccaccc taaaagcacg gggcgcgaac tgtttgccct aaattggctc 780
gaaacctacc ttgacggcgg cgaaaaccga tacgacgtat tgcggacgct ttcccgtttt 840
accgcgcaaa ccgtttgcga cgccgtctca cacgcagcgg cagatgcccg tcaaatgtac 900
atttgcggcg gcggcatccg caatcctgtt ttaatggcgg atttggcaga atgtttcggc 960
acacgcgttt ccctgcacag caccgccgac ctgaacctcg atccgcaatg ggtggaagcc 1020
gccgcatttg cgtggttggc ggcgtgttgg attaatcgca ttcccggtag tccgcacaaa 1080
gcaaccggcg catccaaacc gtgtattctg ggcgcgggat attattattg a 1131
<210> 58
<211> 376
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0377 protein sequence
<400> 58
Met Ala Phe Cys Thr Ser Leu Gly Val Met Met Glu Thr Gln Leu Tyr
1 5 10 15
Ile Gly Ile Met Ser Gly Thr Ser Met Asp Gly Ala Asp Ala Val Leu
20 25 30
Ile Arg Met Asp Gly Gly Lys Trp Leu Gly Ala Glu Gly His Ala Phe
35 40 45
Thr Pro Tyr Pro Gly Arg Leu Arg Arg Gln Leu Leu Asp Leu Gln Asp
50 55 60
Thr Gly Ala Asp Glu Leu His Arg Ser Arg Ile Leu Ser Gln Glu Leu
65 70 75 80
Ser Arg Leu Tyr Ala Gln Thr Ala Ala Glu Leu Leu Cys Ser Gln Asn
85 90 95
Leu Ala Pro Ser Asp Ile Thr Ala Leu Gly Cys His Gly Gln Thr Val
100 105 110
Arg His Ala Pro Glu His Gly Tyr Ser Ile Gln Leu Ala Asp Leu Pro
115 120 125
Leu Leu Ala Glu Arg Thr Arg Ile Phe Thr Val Gly Asp Phe Arg Ser
130 135 140
Arg Asp Leu Ala Ala Gly Gly Gln Gly Ala Pro Leu Val Pro Ala Phe
145 150 155 160
His Glu Ala Leu Phe Arg Asp Asn Arg Glu Thr Arg Ala Val Leu Asn
165 170 175
Ile Gly Gly Ile Ala Asn Ile Ser Val Leu Pro Pro Asp Ala Pro Ala
180 185 190
Phe Gly Phe Asp Thr Gly Pro Gly Asn Met Leu Met Asp Ala Trp Thr
195 200 205
Gln Ala His Trp Gln Leu Pro Tyr Asp Lys Asn Gly Ala Lys Ala Ala
210 215 220
Gln Gly Asn Ile Leu Pro Gln Leu Leu Asp Arg Leu Leu Ala His Pro
225 230 235 240
Tyr Phe Ala Gln Pro His Pro Lys Ser Thr Gly Arg Glu Leu Phe Ala
245 250 255
Leu Asn Trp Leu Glu Thr Tyr Leu Asp Gly Gly Glu Asn Arg Tyr Asp
260 265 270
Val Leu Arg Thr Leu Ser Arg Phe Thr Ala Gln Thr Val Cys Asp Ala
275 280 285
Val Ser His Ala Ala Ala Asp Ala Arg Gln Met Tyr Ile Cys Gly Gly
290 295 300
Gly Ile Arg Asn Pro Val Leu Met Ala Asp Leu Ala Glu Cys Phe Gly
305 310 315 320
Thr Arg Val Ser Leu His Ser Thr Ala Asp Leu Asn Leu Asp Pro Gln
325 330 335
Trp Val Glu Ala Ala Ala Phe Ala Trp Leu Ala Ala Cys Trp Ile Asn
340 345 350
Arg Ile Pro Gly Ser Pro His Lys Ala Thr Gly Ala Ser Lys Pro Cys
355 360 365
Ile Leu Gly Ala Gly Tyr Tyr Tyr
370 375
<210> 59
<211> 1857
<212> DNA
<213> Neisseria meningitidis serogroup B NMB0264 DNA sequence
<400> 59
atgttgaaca aaatattttc ctggttcgag tcccgaatcg acccttatcc cgaagccgcc 60
ccgaaaacgc cagaaaaagg cttgtggcgg tttgtctgga gcagcatggc cggcgtgcgg 120
aaatggatag ccgccctggc tgcgctgacc gccggcatcg gcattatgga agccctggtt 180
tttcaattta tgggcaaaat cgtggagtgg ctcggcaaat acgcgcccgc cgaactgttt 240
gccgaaaaaa gttgggaact ggcggcaatg gcggcgatga tggtattttc ggttgcgtgg 300
gcgtttgccg cgtccaacgt gcgcctgcaa acccttcagg gcgtgttccc catgcgcctg 360
cgctggaact tccaccgcct gatgctgaac caaagcctcg gtttttatca ggacgaattt 420
gccggacgcg tgtccgccaa agtcatgcag accgcgctgg cgttgcgcga cgcggtgatg 480
acggttgccg atatggtcgt ttatgtgtcg gtgtatttca ttacctccgg cgtgattctc 540
gcctcgctcg actcatggct gctgctgccc tttatcggct ggattgtcgg tttcgcttcg 600
gtgatgcgcc tgctgattcc caaattgggg caaaccgccg catggcaggc ggatgcccgc 660
tcgctgatga ccggccgcat taccgatgcc tattccaata tcgccaccgt caaactcttc 720
tcccacggcg cgcgtgaagc cgcctatgcc aagcagtcga tggaagaatt tatggttacg 780
gtgcgcgccc aaatgcggct ggcgacgctg ctgcattcgt gcagcttcat cgtcaacacc 840
tccctgaccc tctccaccgc cgcactgggc atctggctct ggcacaacgg gcaggtcggc 900
gtgggcgcgg ttgctacagc caccgccatg gcgttgcgcg tcaacggttt gtcgcaatac 960
attatgtggg aatccgcgcg gctgtttgaa aacatcggca ccgtcggcga cggcatggca 1020
accctgtcca aaccgcacac catcctcgac aagccccggg cactgccgct gaacgtgccg 1080
caaggcgcaa tcaaatttga acacgtcgat ttctcctacg aagcgggcaa accgctgctc 1140
aacggcttca acctcaccat ccgcccgggc gaaaaagtcg gcttgatcgg acgcagcggc 1200
gcgggcaaat ccaccatcgt caacctgctt ttgcgcttct acgaaccgca aagcggcacg 1260
gtttcgatcg acgggcagga cataagcggc gttacccaag aatctttacg cgcccaaatc 1320
ggtttggtca cgcaagatac ctcgctgctg caccgttccg tgcgcgacaa cattatttac 1380
ggccgccccg acgcgaccga tgccgaaatg gtttctgccg ccgaacgcgc cgaagccgcc 1440
ggcttcatcc ccgacctttc cgatgccaaa gggcggcgcg gctacgacgc acacgtcggc 1500
gaacgcggcg tgaaactctc cggcgggcaa cgccagcgca tcgccatcgc ccgcgtgatg 1560
ctcaaagacg caccgattct tcttttggac gaagccacca gcgcgctcga ttccgaagtc 1620
gaagccgcca tccaagaaag cctcgacaaa atgatggacg gcaaaaccgt catcgccatc 1680
gcccaccgcc tctccaccat cgccgcaatg gacaggctcg tcgtcctcga caaaggccgc 1740
atcatcgaag aaggcacaca cgccgaactc ctcgaaaaac gcgggcttta cgccaaactc 1800
tgggcgcacc agagcggcgg cttcctcaac gaacacgtcg agtggcagca cgactga 1857
<210> 60
<211> 618
<212> PRT
<213> Neisseria meningitidis serogroup B NMB0264 protein sequence
<400> 60
Met Leu Asn Lys Ile Phe Ser Trp Phe Glu Ser Arg Ile Asp Pro Tyr
1 5 10 15
Pro Glu Ala Ala Pro Lys Thr Pro Glu Lys Gly Leu Trp Arg Phe Val
20 25 30
Trp Ser Ser Met Ala Gly Val Arg Lys Trp Ile Ala Ala Leu Ala Ala
35 40 45
Leu Thr Ala Gly Ile Gly Ile Met Glu Ala Leu Val Phe Gln Phe Met
50 55 60
Gly Lys Ile Val Glu Trp Leu Gly Lys Tyr Ala Pro Ala Glu Leu Phe
65 70 75 80
Ala Glu Lys Ser Trp Glu Leu Ala Ala Met Ala Ala Met Met Val Phe
85 90 95
Ser Val Ala Trp Ala Phe Ala Ala Ser Asn Val Arg Leu Gln Thr Leu
100 105 110
Gln Gly Val Phe Pro Met Arg Leu Arg Trp Asn Phe His Arg Leu Met
115 120 125
Leu Asn Gln Ser Leu Gly Phe Tyr Gln Asp Glu Phe Ala Gly Arg Val
130 135 140
Ser Ala Lys Val Met Gln Thr Ala Leu Ala Leu Arg Asp Ala Val Met
145 150 155 160
Thr Val Ala Asp Met Val Val Tyr Val Ser Val Tyr Phe Ile Thr Ser
165 170 175
Gly Val Ile Leu Ala Ser Leu Asp Ser Trp Leu Leu Leu Pro Phe Ile
180 185 190
Gly Trp Ile Val Gly Phe Ala Ser Val Met Arg Leu Leu Ile Pro Lys
195 200 205
Leu Gly Gln Thr Ala Ala Trp Gln Ala Asp Ala Arg Ser Leu Met Thr
210 215 220
Gly Arg Ile Thr Asp Ala Tyr Ser Asn Ile Ala Thr Val Lys Leu Phe
225 230 235 240
Ser His Gly Ala Arg Glu Ala Ala Tyr Ala Lys Gln Ser Met Glu Glu
245 250 255
Phe Met Val Thr Val Arg Ala Gln Met Arg Leu Ala Thr Leu Leu His
260 265 270
Ser Cys Ser Phe Ile Val Asn Thr Ser Leu Thr Leu Ser Thr Ala Ala
275 280 285
Leu Gly Ile Trp Leu Trp His Asn Gly Gln Val Gly Val Gly Ala Val
290 295 300
Ala Thr Ala Thr Ala Met Ala Leu Arg Val Asn Gly Leu Ser Gln Tyr
305 310 315 320
Ile Met Trp Glu Ser Ala Arg Leu Phe Glu Asn Ile Gly Thr Val Gly
325 330 335
Asp Gly Met Ala Thr Leu Ser Lys Pro His Thr Ile Leu Asp Lys Pro
340 345 350
Arg Ala Leu Pro Leu Asn Val Pro Gln Gly Ala Ile Lys Phe Glu His
355 360 365
Val Asp Phe Ser Tyr Glu Ala Gly Lys Pro Leu Leu Asn Gly Phe Asn
370 375 380
Leu Thr Ile Arg Pro Gly Glu Lys Val Gly Leu Ile Gly Arg Ser Gly
385 390 395 400
Ala Gly Lys Ser Thr Ile Val Asn Leu Leu Leu Arg Phe Tyr Glu Pro
405 410 415
Gln Ser Gly Thr Val Ser Ile Asp Gly Gln Asp Ile Ser Gly Val Thr
420 425 430
Gln Glu Ser Leu Arg Ala Gln Ile Gly Leu Val Thr Gln Asp Thr Ser
435 440 445
Leu Leu His Arg Ser Val Arg Asp Asn Ile Ile Tyr Gly Arg Pro Asp
450 455 460
Ala Thr Asp Ala Glu Met Val Ser Ala Ala Glu Arg Ala Glu Ala Ala
465 470 475 480
Gly Phe Ile Pro Asp Leu Ser Asp Ala Lys Gly Arg Arg Gly Tyr Asp
485 490 495
Ala His Val Gly Glu Arg Gly Val Lys Leu Ser Gly Gly Gln Arg Gln
500 505 510
Arg Ile Ala Ile Ala Arg Val Met Leu Lys Asp Ala Pro Ile Leu Leu
515 520 525
Leu Asp Glu Ala Thr Ser Ala Leu Asp Ser Glu Val Glu Ala Ala Ile
530 535 540
Gln Glu Ser Leu Asp Lys Met Met Asp Gly Lys Thr Val Ile Ala Ile
545 550 555 560
Ala His Arg Leu Ser Thr Ile Ala Ala Met Asp Arg Leu Val Val Leu
565 570 575
Asp Lys Gly Arg Ile Ile Glu Glu Gly Thr His Ala Glu Leu Leu Glu
580 585 590
Lys Arg Gly Leu Tyr Ala Lys Leu Trp Ala His Gln Ser Gly Gly Phe
595 600 605
Leu Asn Glu His Val Glu Trp Gln His Asp
610 615
<210> 61
<211> 1410
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1036 DNA sequence
<400> 61
atgacagcac aaaccctcta cgacaaactt tggaacagcc acgtcgtccg cgaagaagaa 60
gacggcaccg tcctgctcta catcgaccgc catttggtgc acgaagttac cagccctcag 120
gcatttgaag gcttgaaaat ggcggggcgc aagctgtggc gcatcgacag cgtcgtctcc 180
accgccgacc acaacacccc gaccggcgat tgggacaaag gcatccaaga cccgatttcc 240
aagctgcaag tcgatacttt ggacaaaaac attaaagagt ttggcgcact cgcctatttt 300
ccgtttatgg acaaaggtca gggcatcgta cacgttatgg gccccgaaca aggcgcgacc 360
ctgcccggta tgaccgtcgt ctgcggcgac tcgcacactt ccacccacgg cgcattcggc 420
gcactggcgc acggcatcgg cacttccgaa gtcgagcaca ccatggcgac ccaatgtatt 480
accgcgaaaa aatccaaatc catgctgatt tccgttgacg gcaaattaaa agcgggcgtt 540
accgccaaag acgtggcgct ctacatcatc gggcaaatcg gcacggcagg cggtacaggc 600
tacgccatcg agtttggcgg cgaagccatc cgcagccttt ctatggaaag ccgcatgact 660
ttatgcaata tggcgattga ggcaggcgcg cgctcaggca tggttgccgt cgaccaaacc 720
accatcgact acgtaaaaga taaacccttc gcacccgaag gcgaagcgtg ggacaaagcc 780
gtcgagtact ggcgtacgct ggtgtctgac gaaggtgcgg tattcgacaa agaataccgt 840
ttcaacgccg aagacatcga accgcaagtc acttggggta cctcgcctga aatggtttta 900
gacatcagca gcaaagtgcc gaatcctgcc gaagaaaccg atccggtcaa acgcagcggt 960
atggaacgcg cccttgaata catgggcttg gaagccggta cgccattaaa cgaaatcccc 1020
gtcgacatcg tattcatcgg ctcttgcacc aacagccgca tcgaagactt gcgcgaagcc 1080
gccgccatcg ccaaagaccg caaaaaagcc gccaacgtac agcgcgtgtt aatcgtcccc 1140
ggctccggtt tggttaaaga acaagccgaa aaagaaggct tggacaaaat tttcatcgaa 1200
gccggttttg aatggcgcga accgggctgt tcgatgtgtc tcgccatgaa cgccgaccgc 1260
ctgaccccgg ggcaacgctg cgcctccacc tccaaccgta actttgaagg ccgtcaaggc 1320
aacggcggac gtacccacct cgtcagcccc gctatggcag cagccgccgc cgttaccggc 1380
cgctttaccg acatccgcat gatggcgtaa 1410
<210> 62
<211> 469
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1036 protein sequence
<400> 62
Met Thr Ala Gln Thr Leu Tyr Asp Lys Leu Trp Asn Ser His Val Val
1 5 10 15
Arg Glu Glu Glu Asp Gly Thr Val Leu Leu Tyr Ile Asp Arg His Leu
20 25 30
Val His Glu Val Thr Ser Pro Gln Ala Phe Glu Gly Leu Lys Met Ala
35 40 45
Gly Arg Lys Leu Trp Arg Ile Asp Ser Val Val Ser Thr Ala Asp His
50 55 60
Asn Thr Pro Thr Gly Asp Trp Asp Lys Gly Ile Gln Asp Pro Ile Ser
65 70 75 80
Lys Leu Gln Val Asp Thr Leu Asp Lys Asn Ile Lys Glu Phe Gly Ala
85 90 95
Leu Ala Tyr Phe Pro Phe Met Asp Lys Gly Gln Gly Ile Val His Val
100 105 110
Met Gly Pro Glu Gln Gly Ala Thr Leu Pro Gly Met Thr Val Val Cys
115 120 125
Gly Asp Ser His Thr Ser Thr His Gly Ala Phe Gly Ala Leu Ala His
130 135 140
Gly Ile Gly Thr Ser Glu Val Glu His Thr Met Ala Thr Gln Cys Ile
145 150 155 160
Thr Ala Lys Lys Ser Lys Ser Met Leu Ile Ser Val Asp Gly Lys Leu
165 170 175
Lys Ala Gly Val Thr Ala Lys Asp Val Ala Leu Tyr Ile Ile Gly Gln
180 185 190
Ile Gly Thr Ala Gly Gly Thr Gly Tyr Ala Ile Glu Phe Gly Gly Glu
195 200 205
Ala Ile Arg Ser Leu Ser Met Glu Ser Arg Met Thr Leu Cys Asn Met
210 215 220
Ala Ile Glu Ala Gly Ala Arg Ser Gly Met Val Ala Val Asp Gln Thr
225 230 235 240
Thr Ile Asp Tyr Val Lys Asp Lys Pro Phe Ala Pro Glu Gly Glu Ala
245 250 255
Trp Asp Lys Ala Val Glu Tyr Trp Arg Thr Leu Val Ser Asp Glu Gly
260 265 270
Ala Val Phe Asp Lys Glu Tyr Arg Phe Asn Ala Glu Asp Ile Glu Pro
275 280 285
Gln Val Thr Trp Gly Thr Ser Pro Glu Met Val Leu Asp Ile Ser Ser
290 295 300
Lys Val Pro Asn Pro Ala Glu Glu Thr Asp Pro Val Lys Arg Ser Gly
305 310 315 320
Met Glu Arg Ala Leu Glu Tyr Met Gly Leu Glu Ala Gly Thr Pro Leu
325 330 335
Asn Glu Ile Pro Val Asp Ile Val Phe Ile Gly Ser Cys Thr Asn Ser
340 345 350
Arg Ile Glu Asp Leu Arg Glu Ala Ala Ala Ile Ala Lys Asp Arg Lys
355 360 365
Lys Ala Ala Asn Val Gln Arg Val Leu Ile Val Pro Gly Ser Gly Leu
370 375 380
Val Lys Glu Gln Ala Glu Lys Glu Gly Leu Asp Lys Ile Phe Ile Glu
385 390 395 400
Ala Gly Phe Glu Trp Arg Glu Pro Gly Cys Ser Met Cys Leu Ala Met
405 410 415
Asn Ala Asp Arg Leu Thr Pro Gly Gln Arg Cys Ala Ser Thr Ser Asn
420 425 430
Arg Asn Phe Glu Gly Arg Gln Gly Asn Gly Gly Arg Thr His Leu Val
435 440 445
Ser Pro Ala Met Ala Ala Ala Ala Ala Val Thr Gly Arg Phe Thr Asp
450 455 460
Ile Arg Met Met Ala
465
<210> 63
<211> 402
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1176 DNA sequence
<400> 63
atgaaagaca agcacgattc ttccgccatg cggctggaca aatggctttg ggcggcacgt 60
tttttcaaga cccgttccct tgcgcaaaag cacatcgaac tgggtagggt tcaagtaaac 120
ggctcgaagg tcaaaaacag taaaaccata gacatcggcg atattatcga cctgacgctc 180
aattcccttc cctataaaat caaggttaaa ggtttgaacc accaacgccg cccggcatcc 240
gaggcgcggc ttctgtatga agaggacgcg aaaacggcaa cattgaggga agagcgcaaa 300
cagctcgacc aattcagccg catcacttcc gcctatcccg acggcagacc gaccaagcgc 360
gaccgccgcc aactggacag gctgaaaaaa ggagactggt aa 402
<210> 64
<211> 133
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1176 protein sequence
<400> 64
Met Lys Asp Lys His Asp Ser Ser Ala Met Arg Leu Asp Lys Trp Leu
1 5 10 15
Trp Ala Ala Arg Phe Phe Lys Thr Arg Ser Leu Ala Gln Lys His Ile
20 25 30
Glu Leu Gly Arg Val Gln Val Asn Gly Ser Lys Val Lys Asn Ser Lys
35 40 45
Thr Ile Asp Ile Gly Asp Ile Ile Asp Leu Thr Leu Asn Ser Leu Pro
50 55 60
Tyr Lys Ile Lys Val Lys Gly Leu Asn His Gln Arg Arg Pro Ala Ser
65 70 75 80
Glu Ala Arg Leu Leu Tyr Glu Glu Asp Ala Lys Thr Ala Thr Leu Arg
85 90 95
Glu Glu Arg Lys Gln Leu Asp Gln Phe Ser Arg Ile Thr Ser Ala Tyr
100 105 110
Pro Asp Gly Arg Pro Thr Lys Arg Asp Arg Arg Gln Leu Asp Arg Leu
115 120 125
Lys Lys Gly Asp Trp
130
<210> 65
<211> 1011
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1359 DNA sequence
<400> 65
atgaaccaca ccgttaccct gcccgaccaa accacctttg ccgccaacga cggcgaaacc 60
gttttgaccg ctgccgcccg tcaaaacctc aacctgcccc attcctgcaa aagcggtgtc 120
tgcggacaat gcaaagccga actggtcagc ggcgatattc aaatgggcgg acactcggaa 180
caggctttat ccgaagcaga aaaagcgcaa ggcaagattt tgatgtgctg caccactgcg 240
caaagcgata tcaacatcaa catccccggc tacaaagccg atgccctacc cgtccgcacc 300
ctgcccgcac gcatcgaaag tattattttc aaacacgatg tcgccctcct gaaacttgcc 360
ctgcccaaag ccccgccgtt tgccttctac gccgggcaat acattgattt actgctgccg 420
ggcaacgtca gccgcagcta ctccatcgcc aatttacccg accaagaagg cattttggaa 480
ctgcacatcc gcaggcacga aaacggtgtc tgctcggaaa tgattttcgg cagcgaaccc 540
aaagtcaaag aaaaaggcat cgtccgcgtt aaaggcccgc tcggttcgtt taccttgcag 600
gaagacagcg gcaaacccgt catcctgctg gcaaccggca caggctacgc ccccatccgc 660
agcatcctgc tcgaccttat ccgccaaggc agcaaccgcg ccgtccattt ctactggggc 720
gcgcgtcatc aggatgattt gtatgccctc gaagaagcac aagggttggc atgccgtctg 780
aaaaacgcct gcttcacccc cgtattgtcc cgccccggag agggctggca gggaagaaat 840
ggtcacgtac aagacatcgc ggcacaagac caccccgacc tgtcggaata cgaagtattt 900
gcctgcggtt ctccggccat gaccgaacaa acaaagaatc tgtttgtgca acagcataag 960
ctgccggaaa acttgttttt ctccgacgca ttcacgccgt ccgcatcata a 1011
<210> 66
<211> 336
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1359 protein sequence
<400> 66
Met Asn His Thr Val Thr Leu Pro Asp Gln Thr Thr Phe Ala Ala Asn
1 5 10 15
Asp Gly Glu Thr Val Leu Thr Ala Ala Ala Arg Gln Asn Leu Asn Leu
20 25 30
Pro His Ser Cys Lys Ser Gly Val Cys Gly Gln Cys Lys Ala Glu Leu
35 40 45
Val Ser Gly Asp Ile Gln Met Gly Gly His Ser Glu Gln Ala Leu Ser
50 55 60
Glu Ala Glu Lys Ala Gln Gly Lys Ile Leu Met Cys Cys Thr Thr Ala
65 70 75 80
Gln Ser Asp Ile Asn Ile Asn Ile Pro Gly Tyr Lys Ala Asp Ala Leu
85 90 95
Pro Val Arg Thr Leu Pro Ala Arg Ile Glu Ser Ile Ile Phe Lys His
100 105 110
Asp Val Ala Leu Leu Lys Leu Ala Leu Pro Lys Ala Pro Pro Phe Ala
115 120 125
Phe Tyr Ala Gly Gln Tyr Ile Asp Leu Leu Leu Pro Gly Asn Val Ser
130 135 140
Arg Ser Tyr Ser Ile Ala Asn Leu Pro Asp Gln Glu Gly Ile Leu Glu
145 150 155 160
Leu His Ile Arg Arg His Glu Asn Gly Val Cys Ser Glu Met Ile Phe
165 170 175
Gly Ser Glu Pro Lys Val Lys Glu Lys Gly Ile Val Arg Val Lys Gly
180 185 190
Pro Leu Gly Ser Phe Thr Leu Gln Glu Asp Ser Gly Lys Pro Val Ile
195 200 205
Leu Leu Ala Thr Gly Thr Gly Tyr Ala Pro Ile Arg Ser Ile Leu Leu
210 215 220
Asp Leu Ile Arg Gln Gly Ser Asn Arg Ala Val His Phe Tyr Trp Gly
225 230 235 240
Ala Arg His Gln Asp Asp Leu Tyr Ala Leu Glu Glu Ala Gln Gly Leu
245 250 255
Ala Cys Arg Leu Lys Asn Ala Cys Phe Thr Pro Val Leu Ser Arg Pro
260 265 270
Gly Glu Gly Trp Gln Gly Arg Asn Gly His Val Gln Asp Ile Ala Ala
275 280 285
Gln Asp His Pro Asp Leu Ser Glu Tyr Glu Val Phe Ala Cys Gly Ser
290 295 300
Pro Ala Met Thr Glu Gln Thr Lys Asn Leu Phe Val Gln Gln His Lys
305 310 315 320
Leu Pro Glu Asn Leu Phe Phe Ser Asp Ala Phe Thr Pro Ser Ala Ser
325 330 335
<210> 67
<211> 402
<212> DNA
<213> Neisseria meningitidis serogroup B NMB1138 DNA sequence
<400> 67
atgaaagaca agcacgattc ttccgccatg cggctggaca aatggctttg ggcggcacgt 60
tttttcaaga cccgttccct tgcgcaaaag cacatcgaac tgggtagggt tcaagtaaac 120
ggctcgaagg tcaaaaacag taaaaccata gacatcggcg atattatcga cctgacgctc 180
aattcccttc cctataaaat caaggttaaa ggtttgaacc accaacgccg cccggcatcc 240
gaggcgcggc ttctgtatga agaggacgcg aaaacggcaa cattgaggga agagcgcaaa 300
cagctcgacc aattcagccg catcacttcc gcctatcccg acggcagacc gaccaagcgc 360
gaccgccgcc aactggacag gctgaaaaaa ggagactggt aa 402
<210> 68
<211> 133
<212> PRT
<213> Neisseria meningitidis serogroup B NMB1138 protein sequence
<400> 68
Met Lys Asp Lys His Asp Ser Ser Ala Met Arg Leu Asp Lys Trp Leu
1 5 10 15
Trp Ala Ala Arg Phe Phe Lys Thr Arg Ser Leu Ala Gln Lys His Ile
20 25 30
Glu Leu Gly Arg Val Gln Val Asn Gly Ser Lys Val Lys Asn Ser Lys
35 40 45
Thr Ile Asp Ile Gly Asp Ile Ile Asp Leu Thr Leu Asn Ser Leu Pro
50 55 60
Tyr Lys Ile Lys Val Lys Gly Leu Asn His Gln Arg Arg Pro Ala Ser
65 70 75 80
Glu Ala Arg Leu Leu Tyr Glu Glu Asp Ala Lys Thr Ala Thr Leu Arg
85 90 95
Glu Glu Arg Lys Gln Leu Asp Gln Phe Ser Arg Ile Thr Ser Ala Tyr
100 105 110
Pro Asp Gly Arg Pro Thr Lys Arg Asp Arg Arg Gln Leu Asp Arg Leu
115 120 125
Lys Lys Gly Asp Trp
130
Claims (9)
- 서열번호 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68 중의 임의의 하나로부터 선택된 아미노산 서열을 포함하는 폴리펩티드; 또는 이의 단편 또는 변이체 또는 상기 단편 또는 변이체의 융합체.
- 제 1 항에 따른 폴리펩티드를 코딩하는 폴리뉴클레오티드.
- 의약에 이용하기 위한 제 1 항에 따른 폴리펩티드 또는 제 2 항에 따른 폴리뉴클레오티드.
- 백신에 이용하기 위한 제 1 항에 따른 폴리펩티드 또는 제 2 항에 따른 폴리뉴클레오티드.
- 숙주 세포에서 제 2 항의 폴리뉴클레오티드를 발현하는 단계 및 폴리펩티드를 분리하는 단계를 포함하는 제 1 항에 따른 폴리펩티드의 제조 방법.
- 폴리펩티드를 화학적으로 합성하는 단계를 포함하는 제 1 항에 따른 폴리펩티드의 제조 방법.
- 제 1 항에 따른 폴리펩티드 또는 제 2 항에 따른 폴리뉴클레오티드를 개인에게 투여하는 단계를 포함하는 수막구균 (Neisseria meningitidis)에 대한 개인의 예방접종 방법.
- 수막구균에 대해 개인을 예방접종하기 위한 백신을 제조하는데 있어서, 제 1 항에 따른 폴리펩티드 또는 제 2 항에 따른 폴리뉴클레오티드의 용도.
- 제 1 항에 따른 폴리펩티드 또는 제 2 항에 따른 폴리뉴클레오티드, 및 약학적으로 허용가능한 담체를 포함하는 약학 조성물.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/GB2004/005441 WO2005060995A2 (en) | 2003-12-23 | 2004-12-23 | Identification of antigenically important neisseria antigens by screening insertional mutant libraries with antiserum |
| GBPCT/GB2004/005441 | 2004-12-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20070094762A true KR20070094762A (ko) | 2007-09-21 |
Family
ID=36282716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077015481A KR20070094762A (ko) | 2004-12-23 | 2005-12-23 | 수막구균에 대한 백신 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1848457A2 (ko) |
| JP (1) | JP2008525008A (ko) |
| KR (1) | KR20070094762A (ko) |
| CN (2) | CN101115502A (ko) |
| AU (1) | AU2005317835A1 (ko) |
| CA (1) | CA2592156A1 (ko) |
| MX (1) | MX2007007886A (ko) |
| NO (1) | NO20073256L (ko) |
| RU (1) | RU2007127921A (ko) |
| WO (1) | WO2006067518A2 (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006328153A1 (en) * | 2005-12-23 | 2007-06-28 | Imperial Innovations Limited | Neisseria meningitidis vaccines and their use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9814902D0 (en) * | 1998-07-10 | 1998-09-09 | Univ Nottingham | Screening of neisserial vaccine candidates against pathogenic neisseria |
-
2005
- 2005-12-23 RU RU2007127921/13A patent/RU2007127921A/ru not_active Application Discontinuation
- 2005-12-23 KR KR1020077015481A patent/KR20070094762A/ko not_active Application Discontinuation
- 2005-12-23 JP JP2007547670A patent/JP2008525008A/ja active Pending
- 2005-12-23 AU AU2005317835A patent/AU2005317835A1/en not_active Abandoned
- 2005-12-23 EP EP05823115A patent/EP1848457A2/en not_active Withdrawn
- 2005-12-23 CA CA002592156A patent/CA2592156A1/en not_active Abandoned
- 2005-12-23 MX MX2007007886A patent/MX2007007886A/es unknown
- 2005-12-23 CN CNA2005800479621A patent/CN101115502A/zh active Pending
- 2005-12-23 WO PCT/GB2005/005113 patent/WO2006067518A2/en active Application Filing
-
2006
- 2006-12-21 CN CNA2006800516894A patent/CN101370514A/zh active Pending
-
2007
- 2007-06-25 NO NO20073256A patent/NO20073256L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| MX2007007886A (es) | 2008-01-16 |
| CN101370514A (zh) | 2009-02-18 |
| WO2006067518A2 (en) | 2006-06-29 |
| WO2006067518A3 (en) | 2006-11-23 |
| JP2008525008A (ja) | 2008-07-17 |
| NO20073256L (no) | 2007-09-17 |
| EP1848457A2 (en) | 2007-10-31 |
| CA2592156A1 (en) | 2006-06-29 |
| CN101115502A (zh) | 2008-01-30 |
| AU2005317835A1 (en) | 2006-06-29 |
| RU2007127921A (ru) | 2009-01-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |