KR102638978B1 - Rsv에 대한 백신 - Google Patents
Rsv에 대한 백신 Download PDFInfo
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- KR102638978B1 KR102638978B1 KR1020187003629A KR20187003629A KR102638978B1 KR 102638978 B1 KR102638978 B1 KR 102638978B1 KR 1020187003629 A KR1020187003629 A KR 1020187003629A KR 20187003629 A KR20187003629 A KR 20187003629A KR 102638978 B1 KR102638978 B1 KR 102638978B1
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- South Korea
- Prior art keywords
- ser
- leu
- thr
- val
- asn
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- C—CHEMISTRY; METALLURGY
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
본 발명은 융합-전 형태에서 안정화된 재조합 호흡기 세포융합 바이러스(respiratory syncitial virus, RSV) 융합(F) 폴리펩티드를 포함하는 조성물에 관한 것으로, 여기에서 상기 RSV F 폴리펩티드는 야생형 RSV F 폴리펩티드와 비교하여 적어도 하나의 돌연변이를 포함하는데, 적어도 하나의 돌연변이는 다음으로 구성되는 군으로부터 선택된다: a) 위치 486에서의 아미노산 아스파르트산(D)의 돌연변이, b) 위치 489에서의 아미노산 아스파르트산(D)의 돌연변이, 및 c) 위치 398에서의 아미노산 세린(S) 및/또는 위치 394에서의 아미노산 리신(K)의 돌연변이. 본 발명은 또한 상기 안정한 RSV F 폴리펩티드를 암호화하는 단리된 핵산 분자를 포함하는 조성물에 관한 것이다.
Description
본 발명은 의약 분야에 관한 것이다. 보다 구체적으로, 본 발명은 RSV에 대한 백신에 관한 것이다.
1950년대에 호흡기 세포융합 바이러스(RSV)의 발견 이후, 이 바이러스는 곧 인간에서 하부 및 상부 호흡기도 감염과 연관된 병원균으로 인식되었다. 전 세계적으로, 매년 6,400만 건의 RSV 감염이 발생하고 있으며, 160,000명이 사망하는 것으로 추정된다(2009년 9월 WHO 급성 호흡기 감염 최신정보). 가장 심각한 질환은 특히 미숙아, 노인 및 면역손상된 개체에서 일어난다. 2세 미만의 아동에서, RSV는 가장 흔한 호흡기 병원균으로서, 호흡기 감염으로 인한 입원의 대략 50%를 차지하며, 2 내지 4개월령에서 입원이 정점에 이른다. 거의 모든 아동이 2세까지 RSV에 감염된 적이 있는 것으로 보고된 바 있다. 일생 동안 반복 감염은 비효과적인 자연 면역에 기인한다. 노인에서, RSV 질환 부담은 비-유행성 인플루엔자 A 감염에 의해 야기되는 것과 유사하다.
RSV는 뉴모비리네(pneumovirinae)의 아과에 속하는 파라믹소바이러스이다. 이의 게놈은 중화 항체에 대한 주요 항원 표적인 RSV 당단백질(G) 및 RSV 융합(F) 단백질로 알려진 멤브레인 단백질을 포함하는 다양한 단백질을 암호화한다. F1 단백질의 융합-매개 부분에 대한 항체는 세포에서 바이러스 섭취를 방해하여 중화 효과를 가질 수 있다.
RSV 감염에 대한 백신은 현재 이용 가능하지 않지만 높은 질환 부담으로 인해 요망된다. RSV 융합 당단백질(RSV F)은 매력적인 백신 항원인데, 위에 명시된 바와 같이 인간 혈청에서 중화 항체의 주요 표적이기 때문이다. 따라서, RSV F에 대한 중화 단클론 항체(팔리비주맙)은 중증 질환을 예방할 수 있고 유아에서 예방 목적으로 승인되었다.
RSV F는 불안정한 융합-전 형태로부터 안정한 융합-후 형태로 비가역적 단백질 재접힘에 의해 바이러스와 숙주-세포 멤브레인을 융합한다. 두 형태의 구조 모두가 RSV F(McLellan JS, et al. Science 342, 592-598 (2013); McLellan JS, et al. Nat Struct Mol Biol 17, 248-250 (2010); McLellan JS, et al. Science 340, 1113-1117 (2013); Swanson KA, et al. Proceedings of the National Academy of Sciences of the United States of America 108, 9619-9624 (2011)) 뿐만 아니라, 관련된 파라믹소바이러스로부터의 융합 단백질에서도 결정되어, 이 복잡한 융합 기구의 기전에 대한 이해를 제공한다. 다른 I형 융합 단백질과 마찬가지로, 비활성 전구체 RSV F0는 세포내 성숙 중에 퓨린(furin)-유사 프로테아제에 의한 절단을 필요로 한다. RSV F는 두 개의 퓨린 부위를 포함하며, 이는 3개의 폴리펩티드: F2, p27 및 F1을 유도하는데, 후자는 N-말단에 소수성 융합 펩티드(FP)를 포함한다. 융합-전 형태로부터 융합-후 형태로 재접힘을 위해서는, FP 및 7가 반복 A(heptad repeat A, HRA)를 포함하는 잔기 137 내지 216 사이의 재접힘 영역 1(RR1)이 나선, 루프 및 가닥의 조립체로부터 긴 연속적 나선으로 변환되어야 한다. RR1의 N-말단 분절에 위치한 FP가 다음에 바이러스 멤브레인으로부터 연장되고 표적 세포의 근위 멤브레인에 삽입될 수 있다. 다음에, 융합-전 F 스파이크에서 C-말단 줄기를 형성하고 7가 반복 B(HRB)를 포함하는 재접힘 영역 2(RR2)는 RSV F 헤드의 다른 쪽으로 이동하고 HRA 이중 코일(coiled-coil) 삼합체를 HRB 도메인에 결합시켜 6-나선 다발을 형성한다. 6-나선 다발을 완성하기 위한 RR1 이중 코일의 형성 및 RR2의 이동은 재접힘 과정 중에 일어나는 가장 극적인 구조적 변화이다.
인간 혈청에서 대부분의 중화 항체는 융합-전 형태에 대하여 지시되지만, 그 불안정성으로 인해 융합-전 형태는 용액 및 비리온의 표면 둘 다에서 융합-후 형태로 일찍 재접힘되는 경향을 갖는다. 둘 다 높은 발현 수준을 갖고 안정한 융합-전 형태를 유지하는 RSV F 단백질은 RSV에 대한 서브유닛 또는 벡터-기반 백신에서의 사용을 위한 유망한 후보가 될 것이다.
본 발명은 안정한 재조합 융합-전 호흡기 세포융합 바이러스(RSV) 융합(F) 폴리펩티드, 즉 융합-전 형태에서 안정화된 재조합 RSV F 폴리펩티드를 포함하는 조성물을 제공한다. 본 발명의 RSV F 폴리펩티드는 융합-전 형태 F 단백질에 특이적인 적어도 하나의 에피토프를 포함한다. 특정 구현예에서, 융합-전 RSV F 폴리펩티드는 가용성 융합-전 RSV F 폴리펩티드이다.
본 발명은 또한 안정한 융합-전 RSV F 폴리펩티드를 암호화하는 핵산 분자를 포함하는 조성물을 제공한다.
특정 구현예에서, 핵산 분자는 융합-전 형태에서 안정화된 전체-길이 멤브레인-결합 RSV F 단백질을 암호화한다. 특정 구현예에서, 핵산 분자는 가용성의 안정화된 융합-전 RSV F 폴리펩티드를 암호화한다.
특정 구현예에서, 핵산 분자는 벡터에 존재한다. 특정 구현예에서, RSV F 폴리펩티드를 암호화하는 핵산은 인간 세포에서의 발현을 위해 코돈 최적화된다.
본 발명은 추가로, RSV F 단백질에 대한 면역 반응을 유도하는 데 있어서의 사용을 위한, 특히 백신으로서의 사용을 위한, 본원에 기술되는 조성물을 제공한다.
본 발명은 또한, 본원에 기술되는 조성물의 유효량을 대상에 투여하는 것을 포함하는, 대상에서 항-호흡기 세포융합 바이러스(RSV) 면역 반응을 유도하는 방법에 관한 것이다. 바람직하게는, 유도된 면역 반응은 RSV에 대한 중화 항체 및/또는 RSV에 대한 보호적 면역을 특징으로 한다. 특정 양태에서 본 발명은, 융합-전 RSV F 폴리펩티드, 상기 RSV F 폴리펩티드를 암호화하는 핵산 분자, 및/또는 상기 핵산 분자를 포함하는 벡터를 포함하는 조성물의 유효량을 대상에 투여하는 것을 포함하는, 대상에서 항-호흡기 세포융합 바이러스(RSV) F 단백질 중화 항체를 유도하는 방법에 관한 것이다.
본 발명은 추가로, RSV에 대하여 대상을 백신접종하는 방법을 제공하는데, 이 방법은 본 발명에 따른 조성물을 대상에 투여하는 것을 포함한다.
특정 구현예에서, 조성물은 근육내 투여된다.
특정 구현예에서, 본 발명에 따른 조성물은 대상에 1회보다 많이 투여된다.
본 발명은 또한, 본 발명에 따른 조성물을 대상에 투여하는 것을 포함하는, 예를 들어 대상의 비관 및 폐에서 RSV의 감염 및/또는 복제를 감소시키는 방법을 제공한다. 이는 대상에서 RSV 감염으로부터 야기되는 부작용을 감소시켜, 백신의 투여시 이러한 부작용에 대한 대상의 보호에 기여할 것이다. 특정 구현예에서, RSV 감염의 부작용은 본질적으로 예방, 즉 임상적으로 관련되지 않은 낮은 수준까지 감소될 수 있다.
도 1: 융합-전 형태를 안정화시키는 RSV F 돌연변이. 증가하는 온도에서 열 충격 후 융합-전 형태로 남아있는 표면-발현된 RSV F 돌연변이체의 백분율. 실험은 다양한 농도에서 2 내지 5회 수행되었다. 표시된 에러 바는 독립 실험으로부터 적어도 2개의 데이터 포인트의 표준 편차를 나타낸다.
호흡기 세포융합 바이러스(RSV)의 융합 단백질(F)은, 감염에 요구되는 숙주 세포 멤브레인과 바이러스 멤브레인의 융합에 관여한다. RSV F mRNA는 F0로 지정된 574 아미노산 전구체 단백질로 번역되고, 이는 소포체에서 신호 펩티드 분해효소에 의해 제거되는 N-말단에서의 신호 펩티드 서열(예를 들어, 서열번호: 1의 아미노산 잔기 1 내지 26)을 포함한다. F0은 트랜스-골지에서 세포 프로테아제(특히 퓨린)에 의해 2개의 부위(아미노산 잔기 109/110과 136/137 사이)에서 절단되어, (p27 영역으로도 불리는, 아미노산 잔기 110 내지 136을 포함하는, 짧은 글리코실화된 개재 서열을 제거하고, F1 및 F2로 지정된 2개의 도메인 또는 서브유닛을 생성한다. F1 도메인(아미노산 잔기 137 내지 574)은 이의 N-말단에 소수성 융합 펩티드를 포함하고 C-말단은 막관통(TM)(아미노산 잔기 530 내지 550) 및 세포질 영역(아미노산 잔기 551 내지 574)을 포함한다. F2 도메인(아미노산 잔기 27 내지 109)은 두 개의 이황화 가교에 의해 F1에 공유적으로 연결된다. F1-F2 헤테로이합체는 비리온에서 호모삼합체로서 조립된다.
RSV 감염에 대한 백신은 현재 이용할 수 없지만 요망된다. 인간 혈청에서 대부분의 중화 항체는 융합-전 형태에 대하여 지시되지만, 그 불안정성으로 인해 융합-전 형태는 용액 및 비리온의 표면 둘 다에서 융합-후 형태로 일찍 재접힘되는 경향을 갖는다.
본 발명은 안정한 재조합 융합-전 RSV F 폴리펩티드, 즉 융합-전 형태에서 안정화된 RSV F 폴리펩티드를 포함하는 조성물을 제공하는데, 여기에서 상기 RSV F 폴리펩티드는 야생형 RSV F 폴리펩티드와 비교하여 적어도 하나의 돌연변이를 포함하고, 적어도 하나의 돌연변이는 다음으로 구성되는 군으로부터 선택된다: a) 위치 486에서의 아미노산 아스파르트산(D)의 돌연변이, b) 위치 489에서의 아미노산 아스파르트산(D)의 돌연변이, 또는 c) 위치 398에서의 아미노산 세린(S) 및/또는 위치 394에서의 아미노산 리신(K)의 돌연변이.
특정 구현예에서, RSV F 폴리펩티드는 가용성 RSV 폴리펩티드이다.
본 발명은 추가로, 본원에 기술되는 RSV F 폴리펩티드를 암호화하는, 즉 야생형 RSV F 폴리펩티드와 비교하여 적어도 하나의 돌연변이를 포함하는 RSV F 폴리펩티드를 암호화하는 단리된 핵산 분자를 포함하는 조성물을 제공하는데, 여기에서 적어도 하나의 돌연변이는 다음으로 구성되는 군으로부터 선택된다: a) 위치 486에서의 아미노산 아스파르트산(D)의 돌연변이, b) 위치 489에서의 아미노산 아스파르트산(D)의 돌연변이, 또는 c) 위치 398에서의 아미노산 세린(S) 및/또는 위치 394에서의 아미노산 리신(K)의 돌연변이.
특정 구현예에서, 핵산 분자는 융합-전 형태에서 안정화된 전체-길이 멤브레인-결합 RSV F 단백질을 암호화한다. 조성물의 투여 후, 상기 핵산 분자로부터 발현된 안정한 전체-길이 RSV 단백질은 핵산 분자가 투여되는 대상의 세포의 세포 멤브레인에서 제시될 것이다.
특정 구현예에서, 핵산 분자는 가용성 RSV F 폴리펩티드를 암호화한다.
특정 구현예에서, 본 발명에 따른 폴리펩티드를 암호화하는 핵산 분자는 포유류 세포, 바람직하게는 인간 세포에서의 발현을 위해 코돈-최적화된다. 코돈-최적화의 방법은 알려져 있고 이전에 기술되었다(예를 들어, WO 96/09378). 야생형 서열과 비교하여 적어도 하나의 비-우선적 코돈이 더 우선적인 코돈으로 대체될 경우 서열은 코돈-최적화된 것으로 간주된다. 본원에서, 비-우선적 코돈은 동일한 아미노산을 암호화하는 다른 코돈보다 유기체에서 덜 빈번하게 사용되는 코돈이고, 또한 더 우선적인 코돈은 비-우선적 코돈보다 유기체에서 더 빈번하게 사용되는 코돈이다. 특정 유기체에서 코돈 사용의 빈도는, http://www.kazusa.or.jp/codon에서와 같이, 코돈 빈도 표에서 발견될 수 있다. 바람직하게는 하나보다 많은 비-우선적 코돈이, 바람직하게는 대부분의 또는 모든 비-우선적 코돈이 보다 우선적인 코돈으로 대체된다. 바람직하게는 유기체에서 가장 빈번하게 사용되는 코돈이 코돈-최적화된 서열에 사용된다. 우선적 코돈에 의한 교체는 일반적으로 더 높은 발현을 유도한다.
유전자 코드의 축중(degeneracy)의 결과로 많은 상이한 폴리뉴클레오티드 및 핵산 분자가 동일한 폴리펩티드를 암호화할 수 있다는 것이 당업자에 의해 이해될 것이다. 당업자는 일상적인 기법을 사용하여, 폴리펩티드가 발현되는 임의의 특정 숙주 유기체의 코돈 사용을 반영하도록 핵산 분자에 의해 암호화되는 폴리펩티드 서열에 영향을 주지 않는 뉴클레오티드 치환을 만들 수 있다는 것이, 또한 이해될 것이다. 따라서, 달리 명시되지 않는 한, "아미노산 서열을 암호화하는 뉴클레오티드 서열"은 상호 축중 형태인, 그리고 동일한 아미노산 서열을 암호화하는 모든 뉴클레오티드 서열을 포함한다. RNA 및 단백질을 암호화하는 뉴클레오티드 서열은 인트론을 포함하거나 포함하지 않을 수 있다.
핵산 서열은 일상적인 분자 생물학 기법을 사용하여 클로닝되거나, DNA 합성에 의해 새로 생성될 수 있는데, 이는 DNA 합성 및/또는 분자 클로닝 분야의 사업을 하는 용역 회사(예를 들어, GeneArt, GenScripts, Invitrogen, Eurofins)에 의해 일상적인 절차를 사용하여 수행될 수 있다.
특정 구현예에서, 핵산 분자는 벡터의 일부이다. 따라서, 본 발명은 또한 위에 기술되는 핵산 분자를 포함하는 벡터를 포함하는 조성물을 제공한다. 이러한 벡터는 해당 분야의 당업자에게 잘 알려진 방법에 의해 용이하게 조작될 수 있고, 예를 들어 원핵 및/또는 진핵 세포에서 복제될 수 있도록 설계될 수 있다. 대안적으로, 벡터는 복제될 수 없도록 설계된다. 본 발명에 따른 적절한 벡터는, 예를 들어 Ad26 또는 AD35를 포함하는 아데노벡터, 알파바이러스, 파라믹소바이러스, 백시니아 바이러스, 헤르페스 바이러스, 레트로바이러스 벡터 등이다. 해당 분야의 당업자는 적절한 발현 벡터를 선택하고, 기능적 방식으로 본 발명의 핵산 서열을 삽입할 수 있다.
본 발명에 따라, 놀랍게도 본원에 기술되는 돌연변이가 개별적 또는 조합으로, RSV F 단백질을 융합-전 형태에서 안정화시킬 수 있다는 것이 발견되었다. 본 발명의 조성물에 존재하는 RSV F 폴리펩티드는 이에 따라 야생형 RSV F 단백질과 비교하여, 특히 서열번호: 1의 RSV F 단백질과 비교하여 적어도 하나의 돌연변이를 포함한다.
특정 구현예에서, 안정한 RSV F 폴리펩티드는 전체-길이 RSV F 단백질을 포함한다. 본 발명에 따르면, 전체-길이 RSV F 단백질은 RSV 비리온 내에 존재하지 않는다. 따라서, 본 발명은 재조합으로 발현된 RSV F 폴리펩티드에 관한 것이다.
본 발명의 안정한 융합-전 RSV F 폴리펩티드는 융합-전 형태로, 즉 이들은 융합-전 형태 F 단백질에 특이적인 적어도 하나의 에피토프를 포함한다(나타낸다). 융합-전 형태 F 단백질에 특이적인 에피토프는 융합-후 형태에서는 제시되지 않는 에피토프이다. 임의의 특정 이론에 구애받지 않고, RSV F 단백질의 융합-전 형태는 천연의 RSV 비리온에서 발현되는 RSV F 단백질에서와 동일한 에피토프를 포함할 수 있고, 따라서 보호적 중화 항체를 이끌어내기 위한 이점을 제공할 수 있는 것으로 여겨진다.
특정 구현예에서, 본 발명의 폴리펩티드는, 서열번호: 4의 중쇄 CDR1 영역, 서열번호: 5의 중쇄 CDR2 영역, 서열번호: 6의 중쇄 CDR3 영역 및 서열번호: 7의 경쇄 CDR1 영역, 서열번호: 8의 경쇄 CDR2 영역, 및 서열번호: 9의 경쇄 CDR3 영역을 포함하는 융합-전 특이적 단클론 항체(이하 CR9501로서 언급됨) 및/또는 서열번호: 10의 중쇄 CDR1 영역, 서열번호: 11의 중쇄 CDR2 영역, 서열번호: 12의 중쇄 CDR3 영역 및 서열번호: 13의 경쇄 CDR1 영역, 서열번호: 14의 경쇄 CDR2 영역, 및 서열번호: 15의 경쇄 CDR3 영역을 포함하는 융합-전 특이적 단클론 항체(CR9502로서 언급됨)에 의해 인식되는 적어도 하나의 에피토프를 포함한다. CR9501 및 CR9502는 중쇄 및 경쇄 가변 영역을 포함하고, 따라서 각각 항체 58C5 및 30D8의 결합 특이성을 포함하는데, 이는 앞서 이의 융합-전 형태의 RSV F 단백질에 특이적으로 결합하지만 융합-후 형태에는 그렇지 않은 것을 보여주었다(WO2012/006596 참조).
특정 구현예에서, 융합-전 RSV F 폴리펩티드는 위치 486에서의 아미노산 잔기 아스파르트산(D)의 아스파라긴(N)으로의 돌연변이(D489Y)를 포함한다.
특정 구현예에서, 융합-전 RSV F 폴리펩티드는 위치 489에서의 아미노산 잔기 아스파르트산(D)의 티로신(Y)으로의 돌연변이(D489Y)를 포함한다.
특정 구현예에서, 본 발명에 따른 안정한 융합-전 RSV F 폴리펩티드는 위치 398에서의 아미노산 잔기 세린(S)의 류신(L)으로의 돌연변이(S398L) 및/또는 위치 394에서의 아미노산 잔기 리신(K)의 아르기닌(R)으로의 돌연변이(K394R)를 포함한다. 특정 구현예에서, 안정한 융합-전 RSV F 폴리펩티드는 위치 398에서의 아미노산 잔기 세린(S)의 류신(L)으로의 돌연변이(S398L) 및 위치 394에서의 아미노산 잔기 리신(K)의 아르기닌(R)으로의 돌연변이(K394R)를 포함한다.
본 발명에 따르면, 놀랍게도 이들 돌연변이는 RSV F 단백질을 융합-전 형태에서, 특히 RSV F 단백질이 전체-길이, 멤브레인-결합 RSV F 단백질일 때, 안정화시킬 수 있음을 보여주었다.
특정 구현예에서, 안정화된 RSV F 폴리펩티드는 가용성 RSV F 폴리펩티드이다.
특정 구현예에서, 본 발명은 이에 따라 안정한 가용성 융합-전 RSV F 폴리펩티드를 포함하는 조성물을 제공한다. 특정 구현예에서, RSV F 단백질은 가용성의 분비된 F 단백질(sF)을 생성하도록 막관통(TM) 및 세포질 영역의 결실에 의해 절단된다. TM 영역은 멤브레인 고정 및 삼합체화를 담당하기 때문에, 비고정된 가용성 F 단백질은 전체-길이 단백질보다 상당히 더 불안정하고 융합-후 최종-상태로 용이하게 재접힘될 것이다. 높은 발현 수준 및 높은 안정성을 보이는 안정한 융합-전 형태의 가용성 F 단백질을 얻기 위해서는, 융합-전 형태가 이에 따라 안정화될 필요가 있다. 단백질의 정단에서 2개의 안정화 돌연변이 및 C-말단 이종 삼합체화 도메인으로 안정화된 가용성 RSV F 폴리펩티드는 WO 2014/174018 및 WO2014/202570에 기술되어 있다. 특히, 돌연변이 N67I 및 S215P는 가용성 재조합 RSV F 폴리펩티드를 융합-전 형태에서 안정화시킬 수 있는 것으로 나타났다. 본 발명에 따른 변경은 WO 2014/174018 및 WO2014/202570에 기술된 바와 같이 가용성 RSV F 단백질을 추가로 안정화시킨다.
특정 구현예에서, 본 발명은 이에 따라 가용성 융합-전 RSV F 폴리펩티드를 포함하는 조성물을 제공하는데, 여기에서 RSV F 폴리펩티드는 위에 기술된 변경의 적어도 하나를, 위치 67에서의 아미노산 잔기 아스파라긴(N) 또는 트레오닌(T)의 돌연변이 및/또는 위치 215에서의 아미노산 잔기 세린(S)의 돌연변이와 조합하여 포함한다.
특정 구현예에서, 본 발명의 조성물에서 가용성 융합-전 RSV F 폴리펩티드는 본원에 기술되는 돌연변이의 적어도 하나를, 위치 67에서의 아미노산 잔기 아스파라긴(N) 또는 트레오닌(T)의 이소류신(I)으로의 돌연변이(N/T67I) 및/또는 위치 215에서의 아미노산 잔기 세린(S)의 프롤린(P)으로의 돌연변이(S215P)와 조합하여 포함한다.
특정 구현예에서, 가용성 융합-전 RSV F 폴리펩티드는 WO2014/174018 및 WO2014/202570에 기술된 바와 같이, 절단된 F1 도메인에 연결된 이종 삼합체화 도메인을 추가로 포함한다. 본원에서 사용되는 "절단된" F1 도메인은 전체 길이 F1 도메인이 아닌 F1 도메인을 말하는데, 즉 여기에서는 N-말단 또는 C-말단에서 하나 이상의 아미노산 잔기가 결실되었다. 본 발명에 따르면, 적어도 막관통 도메인 및 세포질 꼬리가 결실되어 가용성 엑토도메인으로서의 발현이 허용된다.
특정 구현예에서, 삼합체화 도메인은 서열번호: 3을 포함하고, 직접적으로 또는 연결기를 통해, RSV F1 도메인의 아미노산 잔기 513에 연결된다.
특정 구현예에서, 연결기는 아미노산 서열 SAIG를 포함한다.
RSV는 두 개의 항원 서브그룹: A 및 B를 갖는 단일 항원형으로서 존재하는 것으로 알려져 있다. 두 그룹의 성숙한 처리된 F 단백질의 아미노산 서열은 약 93% 동일하다. 본 출원 전체에서 사용되는 바와 같이, 아미노산 위치는 A2 균주로부터의 RSV F 단백질의 서열(서열번호: 1)과 관련하여 주어진다. 본 발명에서 사용되는 표현 "RSV F 단백질의 위치 "x"에서의 아미노산"은 이에 따라 서열번호: 1의 RSV A2 균주의 RSV F 단백질에서 위치 "x"에서의 아미노산에 상응하는 아미노산을 의미한다. 본 출원 전체에서 사용되는 넘버링 시스템에서 1은 미성숙 F0 단백질(서열번호: 1)의 N-말단 아미노산을 의미하는 것임이 주목된다. A2 균주 이외의 RSV 균주가 사용될 때, F 단백질의 아미노산 위치는, 필요시 갭이 삽입된 서열번호: 1의 F 단백질에 다른 RSV 균주의 서열을 정렬하는 것에 의해, 서열번호: 1의 A2 균주의 F 단백질의 넘버링을 참고하여 넘버링된다. 서열 정렬은 해당 분야에 잘 알려진 방법을 사용하여, 예를 들어 CLUSTALW, Bioedit 또는 CLC Workbench에 의해 수행될 수 있다.
본 발명에 따른 아미노산은 천연적으로 존재하는 임의의 20개(또는 '표준' 아미노산) 또는, 예를 들어 D-아미노산(키랄 중심을 갖는 아미노산의 D-거울상이성질체)과 같은 이의 변이체, 또는, 예를 들어 노르류신과 같은, 단백질에서 천연적으로 발견되지 않는 임의의 변이체일 수 있다. 표준 아미노산은 이들의 특성을 기반으로 몇 개의 군으로 분류될 수 있다. 중요한 인자는 전하, 친수성 또는 소수성, 크기 및 기능기이다. 이들 특성은 단백질 구조 및 단백질-단백질 상호작용에 중요하다. 다른 시스테인 잔기와 공유적 이황화 결합(또는 이황화 가교)를 형성할 수 있는 시스테인, 폴리펩티드 골격의 방향전환을 유도하는 프롤린, 그리고 다른 아미노산보다 더 유연한 글리신과 같이, 일부 아미노산은 특별한 특성을 갖는다. 표 1은 표준 아미노산의 약어 및 특성을 보여준다.
일상적인 분자 생물학 절차에 의해 단백질에 돌연변이가 만들어질 수 있음은 당업자에 의해 인정될 것이다. 본 발명에 따른 조성물에서 융합-전 RSV F 폴리펩티드는 안정적, 즉, 예를 들어 정제, 동결-해동 주기, 및/또는 저장 등과 같은 폴리펩티드의 처리시 융합-후 형태로 쉽게 변화되지 않는다.
특정 구현예에서, 본 발명에 따른 융합-전 RSV F 폴리펩티드는, 상기 돌연변이(들)가 없는 RSV F 폴리펩티드와 비교하여, 열을 받을 때 증가된 안정성을 갖는다. 특정 구현예에서, 융합-전 RSV F 폴리펩티드는 55℃의 온도에서, 바람직하게는 58℃에서, 더욱 바람직하게는 60℃에서 적어도 10분 동안 열 안정성이다. "열 안정성"은, 예를 들어 실시예 1에서 기술하는 방법을 사용하여 결정되는 바와 같이, 폴리펩티드가 적어도 10분 동안 증가된 온도(즉, 55℃ 이상의 온도)로 처리된 후 적어도 하나의 융합-전 특이적 에피토프를 여전히 보여주는 것을 의미한다.
특정 구현예에서, RSV F 폴리펩티드는 RSV A 균주로부터 유래된다. 특정 구현예에서 RSV F 폴리펩티드는 서열번호: 1의 RSV A2 균주로부터 유래된다.
특정 구현예에서, RSV F 폴리펩티드는 RSV B 균주로부터 유래된다. 특정 구현예에서 F1 및/또는 F2 도메인은 서열번호: 2의 RSV B 균주로부터 유래된다.
특정의 바람직한 구현예에서, 본 발명의 융합-전 RSV F 폴리펩티드는 서열번호: 21 내지 26으로 구성되는 군으로부터 선택되는 아미노산 서열을 포함한다.
본 출원 전체에서 사용되는 뉴클레오티드 서열은, 해당 분야에서의 관습대로, 5'에서 3' 방향으로, 그리고 아미노산 서열은 N-말단에서 C-말단으로 제공된다.
특정 구현예에서, 본 발명에 따른 폴리펩티드는 서열번호: 1의 아미노산 1 내지 26 또는 서열번호: 2의 아미노산 1 내지 26에 상응하는, 신호 서열 또는 신호 펩티드로도 불리는 리더 서열을 추가로 포함한다. 이것은 분비 경로를 향하도록 예정된, 대부분의 새로 합성된 단백질의 N-말단에 존재하는 짧은(전형적으로 5 내지 30 아미노산 길이) 펩티드이다. 특정 구현예에서, 본 발명에 따른 폴리펩티드는 리더 서열을 포함하지 않는다.
특정 구현예에서, 폴리펩티드는 HIS-태그를 포함한다. His-태그 또는 폴리히스티딘-태그는, 일반적으로 정제 목적을 위해 사용되는, 종종 단백질의 N- 또는 C-말단에서의 적어도 5 히스티딘(H) 잔기로 구성되는 단백질에서의 아미노산 모티프이다.
본원에 기술되는 바와 같이, 본 발명은 안정한 융합-전 RSV F 폴리펩티드, 즉, RSV F 단백질의 융합-전 형태에서 존재하지만 융합-후 형태에는 없는 에피토프를 보여주는 RSV F 폴리펩티드 및/또는 이러한 안정한 융합-전 RSV F 폴리펩티드를 암호화하는 핵산 분자를 포함하는 조성물을 제공한다.
본 발명은 추가로, 본원에 기술되는 것과 같은 융합-전 RSV F 폴리펩티드, 핵산 분자 및/또는 벡터, 그리고 약제학적으로 허용 가능한 담체 또는 부형제를 포함하는 약제학적 조성물을 제공한다. 본 맥락에서, 용어 "약제학적으로 허용 가능한"은 담체 또는 부형제가 이용되는 투여량 및 농도에서 이들이 투여되는 대상에 임의의 원치 않거나 유해한 효과를 야기하지 않을 것을 의미한다. 이러한 약제학적으로 허용 가능한 담체 및 부형제는 해당 분야에 잘 알려져 있다(Remington's Pharmaceutical Sciences, 18th edition, A. R. Gennaro, Ed., Mack Publishing Company [1990]; Pharmaceutical Formulation Development of Peptides and Proteins, S. Frokjaer and L. Hovgaard, Eds., Taylor & Francis [2000]; 및 Handbook of Pharmaceutical Excipients, 3rd edition, A. Kibbe, Ed., Pharmaceutical Press [2000] 참조). RSV F 폴리펩티드, 또는 핵산 분자는, 일부의 경우 동결건조 제제를 이용하는 것도 가능할 수 있지만, 바람직하게는 멸균 용액으로 제형화되고 투여된다. 멸균 용액은 멸균 여과에 의하거나 해당 분야에 그 자체로 알려진 다른 방법에 의해 제조된다. 이어서, 용액은 동결건조되거나 약제학적 투약 용기에 충전된다. 용액의 pH는 일반적으로 pH 3.0 내지 9.5, 예를 들어 pH 5.0 내지 7.5의 범위이다. RSV F 폴리펩티드는 전형적으로 약제학적으로 허용 가능한 적절한 완충액을 갖는 용액에 존재하고, 조성물은 또한 염을 포함할 수 있다. 특정 구현예에서, RSV F 폴리펩티드는 주사 가능한 제제로 제형화될 수 있다.
본 발명에 따른 조성물의 유효량을 대상에 투여하는 것을 포함하는, 대상에서 RSV F 단백질에 대한 면역 반응을 유도하는 방법이 추가로 제공된다. 대상에서 RSV F 단백질에 대한 면역 반응을 유도하는 데 있어서의 사용을 위한, 특히 백신으로서의 사용을 위한, 본 발명에 따른 조성물이 또한 제공된다. 대상에서 RSV F 단백질에 대한 면역 반응을 유도하는 데 있어서의 사용을 위한 약제의 제조를 위한 본 발명에 따른 조성물의 용도가 추가로 제공된다. 바람직하게는, 유도된 면역 반응은 RSV에 대한 중화 항체 및/또는 RSV에 대한 보호적 면역을 특징으로 한다.
특정의 양태에서, 본 발명은 본원에 기술되는 조성물의 유효량을 대상에 투여하는 것을 포함하는, 대상에서 항-호흡기 세포융합 바이러스(RSV) F 단백질 중화 항체를 유도하는 방법에 관한 것이다.
본 발명은 또한, 본 발명에 따른 조성물을 대상에 투여하는 것을 포함하는, 예를 들어 대상의 비관 및 폐에서 RSV의 감염 및/또는 복제를 감소시키는 방법을 제공한다. 이는 대상에서 RSV 감염으로부터 야기되는 부작용을 감소시켜, 백신의 투여시 이러한 부작용에 대한 대상의 보호에 기여할 것이다. 특정 구현예에서, RSV 감염의 부작용은 본질적으로 예방, 즉 임상적으로 관련되지 않은 낮은 수준까지 감소될 수 있다.
본 발명의 조성물은 RSV 감염의 방지(예방) 및/또는 치료를 위해 사용될 수 있다. 특정 구현예에서, 방지 및/또는 치료는 RSV 감염에 취약한 환자군을 표적으로 할 수 있다. 이러한 환자군은, 예를 들어 노인(예를 들어, 50세 이상, 60세 이상, 바람직하게는 65세 이상), 어린이(예를 들어, 5세 이하, 1세 이하), 입원 환자 및 항바이러스 화합물 치료를 받았으나 부적절한 항바이러스 반응을 나타낸 환자를 포함하지만, 이에 한정되는 것은 아니다.
본 발명에 따른 조성물은, 예를 들어 RSV에 의해 야기되는 질환 또는 병태의 독립 치료 및/또는 예방에, 또는 (기존 또는 향후) 백신, 항바이러스제 및/또는 단클론 항체와 같은 다른 예방적 및/또는 치료적 처치와 조합하여 사용될 수 있다.
본 발명은 추가로, 본 발명에 따른 조성물을 이용하여 대상에서 RSV 감염을 예방 및/또는 치료하는 방법을 제공한다. 특정 구현예에서, 대상에서 RSV 감염을 예방 및/또는 치료하는 방법은, 본원에 기술되는 바와 같이, 유효량의 융합-전 RSV F 폴리펩티드, 핵산 분자 및/또는 벡터를 포함하는 조성물을 이를 필요로 하는 대상에 투여하는 것을 포함한다. 치료적으로 유효한 양은 RSV에 의한 감염으로부터 야기되는 질환 또는 병태를 예방, 완화 및/또는 치료하는 데 유효한 폴리펩티드, 핵산 분자 또는 벡터의 양을 말한다. 예방은 RSV의 확산을 억제 또는 감소, 또는 RSV에 의한 감염과 관련되는 하나 이상의 증상의 개시, 발생 또는 진행을 억제 또는 감소시키는 것을 포괄한다. 본원에서 사용되는 완화는 인플루엔자 감염의 가시적 또는 인지할 수 있는 질환 증상, 바이러스 혈증, 또는 임의의 다른 측정 가능한 징후의 감소를 의미할 수 있다.
특정 구현예에서, 본 발명에 따른 조성물은 하나 이상의 애주번트를 추가로 포함한다. 애주번트는 적용되는 항원 결정기에 대한 면역 반응을 더욱 증가시키는 것으로 해당 분야에 알려져 있다. 용어 "애주번트" 및 "면역 자극제"는 본원에서 상호교환적으로 사용되고, 면역계의 자극을 야기하는 하나 이상의 물질로서 정의된다. 이러한 맥락에서, 애주번트는 본 발명의 RSV F 폴리펩티드에 대한 면역 반응을 증진시키기 위해 사용된다. 적절한 애주번트의 예로는 수산화알루미늄 및/또는 인산알루미늄과 같은 알루미늄염; MF59와 같은 스쿠알렌-물 유제를 포함하는 오일-유제 조성물(또는 수중유 조성물)(예를 들어, WO 90/14837 참조); 예를 들어 QS21 및 면역자극 복합체(ISCOMS)와 같은 사포닌 제형(예를 들어, US 5,057,540; WO 90/03184, WO 96/11711, WO 2004/004762, WO 2005/002620 참조); 박테리아 또는 미생물 유도체, 이의 예로 모노포스포릴 리피드 A(MPL), 3-O-탈아실화 MPL(3dMPL), CpG-모티프 함유 올리고뉴클레오티드, ADP-리보실화 박테리아 독소 또는 이의 돌연변이체, 예를 들어 대장균(E. coli) 열 불안정 장독소 LT, 콜레라 독소 CT 등; 진핵 단백질(예를 들어, 항체 또는 이의 단편(예를 들어, 항원 자체 또는 CD1a, CD3, CD7, CD80에 대하여 지시되는) 및, 수용체 세포와의 상호작용시 면역 반응을 자극하는 수용체에 대한 리간드(예를 들어, CD40L, GMCSF, GCSF 등)를 포함한다. 특정 구현예에서, 본 발명의 조성물은 애주번트로서 알루미늄을, 예를 들어 수산화알루미늄, 인산알루미늄, 인산알루미늄칼륨, 또는 이의 조합의 형태로, 용량 당 알루미늄 함량 0.05 내지 5 mg, 예를 들어, 0.075 내지 1.0 mg의 농도로 포함한다.
특정 구현예에서, 본 발명에 따른 조성물은 호흡기 세포융합 바이러스(RSV)에 대한 백신으로서의 용도를 위한 것이다. 용어 "백신"은 특정 병원균 또는 질환에 대하여 대상에서 특정한 정도의 면역성을 유도하는 데 효과적인 활성 성분을 포함하는 조성물을 말하는데, 이는 질환 또는 병원균에 의한 감염과 관련된 증상의 중증도, 지속 기간 또는 다른 징후의 적어도 (완전한 부재까지) 감소를 야기할 것이다. 본 발명에서 백신은, RSV의 F 단백질에 대한 면역 반응을 야기하는, 유효량의 융합-전 RSV F 폴리펩티드 및/또는 융합-전 RSV F 폴리펩티드를 암호화하는 핵산 분자, 및/또는 상기 핵산 분자를 포함하는 벡터를 포함한다. 백신은 입원으로 이어지는 중증의 하부 호흡기도 질환을 예방하고 대상에서 RSV 감염 및 복제에 기인하는 폐렴 및 세기관지염과 같은 합병증의 빈도를 저하시키기 위해 사용될 수 있다. 특정 구현예에서 백신은, 예를 들어 RSV의 다른 단백질 및/또는 다른 감염성 물질에 대한 면역 반응을 유도하는 다른 성분을 추가로 포함하는 조합 백신일 수 있다. 추가의 활성 성분의 투여는, 예를 들어 개별 투여에 의해 또는 본 발명의 백신과 추가의 활성 성분의 조합 제품을 투여하는 것에 의해 행하여질 수 있다.
본 발명은 추가로, RSV에 대하여 대상을 백신접종하는 방법을 제공하는데, 이 방법은 본 발명에 따른 조성물을 대상에 투여하는 것을 포함한다.
본 발명에 따른 조성물은 대상, 예를 들어 인간 대상에 투여될 수 있다. 권고 용량의 결정은 실험에 의해 수행될 것이며 해당 분야의 당업자에게 일상적인 것이다.
본 발명에 따른 조성물의 투여는 표준 투여 경로를 사용하여 수행될 수 있다. 비-제한적 구현예는 비경구 투여, 예를 들어 피부내, 근육내, 피하, 경피, 또는 점막 투여, 예를 들어 비강내, 경구 투여 등을 포함한다. 일 구현예에서 조성물은 근육내 주사에 의해 투여된다. 당업자는 백신에서 항원(들)에 대한 면역 반응을 유도하기 위해 조성물, 예를 들어 백신을 투여하기 위한 다양한 가능성을 알고 있다. 특정 구현예에서, 본 발명의 조성물은 근육내 투여된다.
본원에서 사용되는 대상은 바람직하게는 포유류, 예를 들어 설치류, 예를 들어 마우스, 코튼 랫 또는 비-인간-영장류, 또는 인간이다. 바람직하게는, 대상은 인간 대상이다.
본 발명에 따른 조성물은 동종 또는 이종 프라임-부스트 요법에서 프라임으로서, 또는 부스트로서 투여될 수 있다. 부스팅 백신접종이 수행될 경우, 전형적으로, 이러한 부스팅 백신접종은 조성물을 대상에 최초로 투여한 후(이러한 경우 '프라이밍 백신접종'으로서 언급됨) 1주 내지 1년 사이, 바람직하게는 2주 내지 4개월 사이의 시간에 동일한 대상에 투여될 것이다. 특정 구현예에서, 투여는 프라임 및 적어도 1회의 부스터 투여를 포함한다.
본 발명은 추가로, 야생형 RSV F 단백질과 비교하여, RSV F 단백질에서 돌연변이를 도입하는 것을 포함하는, RSV F 폴리펩티드의 융합-전 형태를 안정화시키는 방법을 제공하는데, 여기에서 하나 이상의 돌연변이는 다음 군으로부터 선택된다:
이러한 방법에 의해 얻을 수 있고/있거나 얻어지는 안정화된 융합-전 RSV F 폴리펩티드뿐만 아니라, 위에 기술된 이의 용도 또한 본 발명의 일부를 형성한다.
본 발명은 다음 실시예에서 추가로 설명된다. 실시예는 어떠한 방식으로도 본 발명을 제한하지 않는다. 이들은 단지 본 발명을 명확하게 하도록 제공된다.
실시예
실시예
1
안정한 융합-전
RSV
F 폴리펩티드의 제조
호흡기 세포융합 바이러스(RSV) F 단백질에 결합하는 치료적 소형 분자는 멤브레인 융합을 억제하고 준안정성 RSV F 융합-전 형태의 중심 강 내에서 3-겹(fold) 대칭 포켓에 결합한다. 억제제 결합은 멤브레인 융합을 용이하게 하는 큰 구조적 재배열을 겪을 필요가 있는 두 영역을 묶음으로써 이 형태를 안정화시킨다. 본 발명에 따르면, 놀랍게도 탈출 돌연변이가 역설적으로 융합-전 형태를 안정화시키는 것이 확인되었다. 따라서, 본 발명에 따르면, 이 계열의 탈출 돌연변이에 상응하는 아미노산 치환이 RSV F를 융합-전 형태에서 안정화시키기 위해 사용될 수 있는 것으로 나타났다.
본 발명으로 이어진 연구에서 온도-기반의 촉발 분석이 융합-전 F 안정성에 대한 돌연변이의 효과를 평가하기 위해 개발되었다. 야생형 RSV F 또는 돌연변이체 RSV F를 발현하는 HEK293 세포를 증가하는 온도에서 10분 동안 열 충격을 주어 녹는 곡선이 결정되도록 하였다. D489Y 변이체와 같은 돌연변이는 촉발에 요구되는 온도를 실질적으로 증가시키고(도 1), 이에 따라 이 돌연변이가 RSV F 폴리펩티드를 안정화시킨 것을 나타낸다. 전체-길이 RSV F 단백질(야생형 및 본 발명에 따른 돌연변이를 하나 이상 포함하는)을 HEK293T 세포에서 일시적으로 발현시켰다. 형질감염-후 48시간에, EDTA-함유 완충액을 사용하여 세포를 탈착시키고 10분 동안 열-충격을 주었다. 세포를 융합-전 RSV F에 특이적이거나(항체 CR9501) 융합-전 및 융합-후 형태 둘 다를 인식하는(항체 CR9503, 이는 RSV F 항체 모타비주맙의 중쇄 및 경쇄 가변 영역을 포함) AlexaFluor647-접합된 항체로 염색하였다. 요오드화프로피듐(Invitrogen)을 라이브-데드(live-dead) 염색으로 사용하고 세포를 FACS Canto II 기기(BD Biosciences)에서 유동세포분석에 의해 분석하였다. 데이터를 FlowJo 9.6 소프트웨어를 사용하여 분석하고 평균 형광 강도(MFI)를 계산하여, 열-충격 샘플을 비처리(37℃) 샘플에 대하여 정규화하였다.
작제물을 Gene Art(Life Technologies, Carlsbad, CA)에서 합성하고 코돈-최적화하였다. 작제물을 pCDNA2004에 클로닝하거나 부위-특이적 돌연변이유발 및 PCR을 수반하는 분야 내에서 널리 알려진 표준 방법에 의해 생성하고 서열화하였다.
서열
RSV
F 단백질 A2 전체 길이 서열(서열번호: 1)
RSV
F 단백질 B1 전체 길이 서열(서열번호: 2)
서열번호: 3
CR9501 중쇄(서열번호: 16):
CR9501 경쇄(서열번호: 17):
CR9502 중쇄(서열번호: 18):
CR9502 경쇄(서열번호: 19):
PreF
,
RSV
A2,
피브리틴
(서열번호: 20)(가용성,
피브리틴이
있는 wt)
PreF
,
RSV
A2,(
서열번호: 21)
D486N
PreF
,
RSV
A2,(
서열번호: 22)
D489Y
PreF
,
RSV
A2,(
서열번호: 23)
S398L
,
K394R
가용성
PreF
,
RSV
A2,(
서열번호: 24)
D486N
가용성
PreF
,
RSV
A2,(
서열번호: 25)
D489Y
가용성
PreF
,
RSV
A2,(
서열번호: 26)
S398L
,
K394R
SEQUENCE LISTING
<110> Janssen Vaccines and Prevention B.V.
<120> Vaccine against RSV
<130> 0257 WO 00 ORD
<160> 26
<170> PatentIn version 3.5
<210> 1
<211> 574
<212> PRT
<213> Artificial Sequence
<220>
<223> RSV F protein A2 full length sequence
<400> 1
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Lys Asn Lys Cys Asn Gly Thr Asp Ala Lys Ile Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
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Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
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Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Val Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 2
<211> 574
<212> PRT
<213> Artificial Sequence
<220>
<223> RSV F protein B1 full length sequence
<400> 2
Met Glu Leu Leu Ile His Arg Leu Ser Ala Ile Phe Leu Thr Leu Ala
1 5 10 15
Ile Asn Ala Leu Tyr Leu Thr Ser Ser Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Arg Gly Tyr Phe Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Thr Lys Cys Asn Gly Thr Asp Thr Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Asn Thr Pro Ala Ala Asn Asn Arg Ala Arg Arg Glu Ala Pro
100 105 110
Gln Tyr Met Asn Tyr Thr Ile Asn Thr Thr Lys Asn Leu Asn Val Ser
115 120 125
Ile Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Ile Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Asn Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asn Asn Gln Leu Leu Pro Ile Val Asn
195 200 205
Gln Gln Ser Cys Arg Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Ser Arg Leu Leu Glu Ile Asn Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Leu Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Ser Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Ile Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Ile Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Asp Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Ser Leu Cys Asn Thr
370 375 380
Asp Ile Phe Asn Ser Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Ile Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Leu Glu Gly
450 455 460
Lys Asn Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Tyr Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Arg Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Thr Gly Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Val Leu Leu Ser Leu Ile Ala Ile
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Lys Asn Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Lys
565 570
<210> 3
<211> 27
<212> PRT
<213> Artificial Sequence
<220>
<223> FIBRITIN
<400> 3
Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln Ala Tyr Val Arg Lys
1 5 10 15
Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
20 25
<210> 4
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 HCDR1
<400> 4
Gly Ala Ser Ile Asn Ser Asp Asn Tyr Tyr Trp Thr
1 5 10
<210> 5
<211> 16
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 HCDR2
<400> 5
His Ile Ser Tyr Thr Gly Asn Thr Tyr Tyr Thr Pro Ser Leu Lys Ser
1 5 10 15
<210> 6
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 HCDR3
<400> 6
Cys Gly Ala Tyr Val Leu Ile Ser Asn Cys Gly Trp Phe Asp Ser
1 5 10 15
<210> 7
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 LCDR1
<400> 7
Gln Ala Ser Gln Asp Ile Ser Thr Tyr Leu Asn
1 5 10
<210> 8
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 LCDR2
<400> 8
Gly Ala Ser Asn Leu Glu Thr
1 5
<210> 9
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 LCDR3
<400> 9
Gln Gln Tyr Gln Tyr Leu Pro Tyr Thr
1 5
<210> 10
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 HCDR1
<400> 10
Gly Phe Thr Phe Ser Gly His Thr Ile Ala
1 5 10
<210> 11
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 HCDR2
<400> 11
Trp Val Ser Thr Asn Asn Gly Asn Thr Glu Tyr Ala Gln Lys Ile Gln
1 5 10 15
Gly
<210> 12
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 HCDR3
<400> 12
Glu Trp Leu Val Met Gly Gly Phe Ala Phe Asp His
1 5 10
<210> 13
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 LCDR1
<400> 13
Gly Ala Asn Asn Ile Gly Ser Gln Asn Val His
1 5 10
<210> 14
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 LCDR2
<400> 14
Asp Asp Arg Asp Arg Pro Ser
1 5
<210> 15
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 LCDR3
<400> 15
Gln Val Trp Asp Ser Ser Arg Asp Gln Ala Val Ile
1 5 10
<210> 16
<211> 228
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 heavy chain
<400> 16
Gln Val Gln Leu Val Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln
1 5 10 15
Thr Leu Ala Leu Thr Cys Asn Val Ser Gly Ala Ser Ile Asn Ser Asp
20 25 30
Asn Tyr Tyr Trp Thr Trp Ile Arg Gln Arg Pro Gly Gly Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Ser Tyr Thr Gly Asn Thr Tyr Tyr Thr Pro Ser
50 55 60
Leu Lys Ser Arg Leu Ser Met Ser Leu Glu Thr Ser Gln Ser Gln Phe
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Ser Ala Val Tyr Phe
85 90 95
Cys Ala Ala Cys Gly Ala Tyr Val Leu Ile Ser Asn Cys Gly Trp Phe
100 105 110
Asp Ser Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ala Ser Thr
115 120 125
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser
130 135 140
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu
145 150 155 160
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His
165 170 175
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
180 185 190
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys
195 200 205
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215 220
Pro Lys Ser Cys
225
<210> 17
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9501 light chain
<400> 17
Glu Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Ile Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Thr Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Thr Gly
50 55 60
Ser Gly Tyr Gly Thr Asp Phe Ser Val Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Gln Tyr Leu Pro Tyr
85 90 95
Thr Phe Ala Pro Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 18
<211> 224
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 heavy chain
<400> 18
Glu Val Gln Leu Leu Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Phe Thr Phe Ser Gly His
20 25 30
Thr Ile Ala Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Val Ser Thr Asn Asn Gly Asn Thr Glu Tyr Ala Gln Lys Ile
50 55 60
Gln Gly Arg Val Thr Met Thr Met Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Trp Leu Val Met Gly Gly Phe Ala Phe Asp His Trp Gly
100 105 110
Gln Gly Thr Leu Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys
210 215 220
<210> 19
<211> 215
<212> PRT
<213> Artificial Sequence
<220>
<223> CR9502 light chain
<400> 19
Gln Ser Val Leu Thr Gln Ala Ser Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Thr Cys Gly Ala Asn Asn Ile Gly Ser Gln Asn Val
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Val Tyr
35 40 45
Asp Asp Arg Asp Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Arg Asp Gln
85 90 95
Ala Val Ile Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro
100 105 110
Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu
115 120 125
Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro
130 135 140
Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala
145 150 155 160
Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala
165 170 175
Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg
180 185 190
Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr
195 200 205
Ile Ala Pro Thr Glu Cys Ser
210 215
<210> 20
<211> 544
<212> PRT
<213> Artificial Sequence
<220>
<223> PreF, RSV A2, fibritin
<400> 20
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
<210> 21
<211> 574
<212> PRT
<213> Artificial Sequence
<220>
<223> PreF, RSV A2, (SEQ ID NO: 21 ) D486N
<400> 21
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asn Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Val Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 22
<211> 574
<212> PRT
<213> Artificial Sequence
<220>
<223> PreF, RSV A2, (SEQ ID NO: 22) D489Y
<400> 22
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Tyr Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Val Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 23
<211> 574
<212> PRT
<213> Artificial Sequence
<220>
<223> PreF, RSV A2, (SEQ ID NO:23) S398L, K394R
<400> 23
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Arg Ile Met Thr Leu Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu His Asn Val Asn Ala Val Lys Ser Thr Thr Asn Ile Met Ile Thr
515 520 525
Thr Ile Ile Ile Val Ile Ile Val Ile Leu Leu Ser Leu Ile Ala Val
530 535 540
Gly Leu Leu Leu Tyr Cys Lys Ala Arg Ser Thr Pro Val Thr Leu Ser
545 550 555 560
Lys Asp Gln Leu Ser Gly Ile Asn Asn Ile Ala Phe Ser Asn
565 570
<210> 24
<211> 544
<212> PRT
<213> Artificial Sequence
<220>
<223> Soluble PreF, RSV A2, (SEQ ID NO: 24) D486N
<400> 24
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asn Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
<210> 25
<211> 544
<212> PRT
<213> Artificial Sequence
<220>
<223> Soluble PreF, RSV A2, (SEQ ID NO: 25) D489Y
<400> 25
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Lys Ile Met Thr Ser Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Tyr Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
<210> 26
<211> 544
<212> PRT
<213> Artificial Sequence
<220>
<223> Soluble PreF, RSV A2, (SEQ ID NO: 26) S398L, K394R
<400> 26
Met Glu Leu Leu Ile Leu Lys Ala Asn Ala Ile Thr Thr Ile Leu Thr
1 5 10 15
Ala Val Thr Phe Cys Phe Ala Ser Gly Gln Asn Ile Thr Glu Glu Phe
20 25 30
Tyr Gln Ser Thr Cys Ser Ala Val Ser Lys Gly Tyr Leu Ser Ala Leu
35 40 45
Arg Thr Gly Trp Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile
50 55 60
Lys Glu Asn Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys
65 70 75 80
Gln Glu Leu Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu
85 90 95
Met Gln Ser Thr Pro Ala Thr Asn Asn Arg Ala Arg Arg Glu Leu Pro
100 105 110
Arg Phe Met Asn Tyr Thr Leu Asn Asn Ala Lys Lys Thr Asn Val Thr
115 120 125
Leu Ser Lys Lys Arg Lys Arg Arg Phe Leu Gly Phe Leu Leu Gly Val
130 135 140
Gly Ser Ala Ile Ala Ser Gly Val Ala Val Ser Lys Val Leu His Leu
145 150 155 160
Glu Gly Glu Val Asn Lys Ile Lys Ser Ala Leu Leu Ser Thr Asn Lys
165 170 175
Ala Val Val Ser Leu Ser Asn Gly Val Ser Val Leu Thr Ser Lys Val
180 185 190
Leu Asp Leu Lys Asn Tyr Ile Asp Lys Gln Leu Leu Pro Ile Val Asn
195 200 205
Lys Gln Ser Cys Ser Ile Ser Asn Ile Glu Thr Val Ile Glu Phe Gln
210 215 220
Gln Lys Asn Asn Arg Leu Leu Glu Ile Thr Arg Glu Phe Ser Val Asn
225 230 235 240
Ala Gly Val Thr Thr Pro Val Ser Thr Tyr Met Leu Thr Asn Ser Glu
245 250 255
Leu Leu Ser Leu Ile Asn Asp Met Pro Ile Thr Asn Asp Gln Lys Lys
260 265 270
Leu Met Ser Asn Asn Val Gln Ile Val Arg Gln Gln Ser Tyr Ser Ile
275 280 285
Met Ser Ile Ile Lys Glu Glu Val Leu Ala Tyr Val Val Gln Leu Pro
290 295 300
Leu Tyr Gly Val Ile Asp Thr Pro Cys Trp Lys Leu His Thr Ser Pro
305 310 315 320
Leu Cys Thr Thr Asn Thr Lys Glu Gly Ser Asn Ile Cys Leu Thr Arg
325 330 335
Thr Asp Arg Gly Trp Tyr Cys Asp Asn Ala Gly Ser Val Ser Phe Phe
340 345 350
Pro Gln Ala Glu Thr Cys Lys Val Gln Ser Asn Arg Val Phe Cys Asp
355 360 365
Thr Met Asn Ser Leu Thr Leu Pro Ser Glu Val Asn Leu Cys Asn Val
370 375 380
Asp Ile Phe Asn Pro Lys Tyr Asp Cys Arg Ile Met Thr Leu Lys Thr
385 390 395 400
Asp Val Ser Ser Ser Val Ile Thr Ser Leu Gly Ala Ile Val Ser Cys
405 410 415
Tyr Gly Lys Thr Lys Cys Thr Ala Ser Asn Lys Asn Arg Gly Ile Ile
420 425 430
Lys Thr Phe Ser Asn Gly Cys Asp Tyr Val Ser Asn Lys Gly Val Asp
435 440 445
Thr Val Ser Val Gly Asn Thr Leu Tyr Tyr Val Asn Lys Gln Glu Gly
450 455 460
Lys Ser Leu Tyr Val Lys Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro
465 470 475 480
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
485 490 495
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
500 505 510
Leu Ser Ala Ile Gly Gly Tyr Ile Pro Glu Ala Pro Arg Asp Gly Gln
515 520 525
Ala Tyr Val Arg Lys Asp Gly Glu Trp Val Leu Leu Ser Thr Phe Leu
530 535 540
Claims (15)
- 융합-전 형태에서 안정화된 재조합 호흡기 세포융합 바이러스(RSV) 융합(F) 폴리펩티드를 포함하는 조성물에 있어서, 상기 RSV F 폴리펩티드는 서열번호:1 또는 서열번호: 2의 아미노산 서열의 야생형 RSV F 폴리펩티드와 비교하여 돌연변이를 포함하고, 상기 돌연변이는 위치 486의 아미노산 아스파르트산(D)에서 아스파라긴(N)으로의 돌연변이인, 조성물.
- 융합-전 형태에서 안정화된 재조합 호흡기 세포융합 바이러스(RSV) 융합(F) 폴리펩티드를 암호화하는 핵산 서열을 포함하는 조성물에 있어서, 상기 RSV F 폴리펩티드는 서열번호:1 또는 서열번호: 2의 아미노산 서열의 야생형 RSV F 폴리펩티드와 비교하여 돌연변이를 포함하고, 상기 돌연변이는 위치 486의 아미노산 아스파르트산(D)에서 아스파라긴(N)으로의 돌연변이인, 조성물.
- 제2항에 있어서, 핵산 서열은 벡터에 포함되는 조성물.
- 삭제
- 삭제
- 삭제
- 제1항 또는 제2항에 있어서, RSV F 폴리펩티드는 전체-길이 RSV F 단백질인 조성물.
- 제1항 또는 제2항에 있어서, RSV F 폴리펩티드는 가용성 RSV F 단백질인 조성물.
- 제1항 또는 제2항에 있어서, 폴리펩티드는 55℃에서 적어도 10분 동안 안정한 조성물.
- 제1항 또는 제2항에 있어서, 폴리펩티드는 서열번호: 21 및 서열번호: 24로 구성되는 군으로부터 선택되는 아미노산 서열을 포함하는 조성물.
- 제1항 또는 제2항에 있어서, RSV F 단백질에 대한 면역 반응을 유도하는 데 있어서의 사용을 위한 조성물.
- 제1항 또는 제2항에 있어서, 백신으로서의 사용을 위한 조성물.
- 제1항 또는 제2항에 있어서, RSV 감염의 예방 및 치료 중 적어도 하나에 사용을 위한 조성물.
- 제1항 또는 제2항에 있어서, 폴리펩티드는 58℃에서 적어도 10분 동안 안정한 조성물.
- 제1항 또는 제2항에 있어서, 폴리펩티드는 60℃에서 적어도 10분 동안 안정한 조성물.
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EP15175647 | 2015-07-07 | ||
EP15175647.5 | 2015-07-07 | ||
PCT/EP2016/066098 WO2017005844A1 (en) | 2015-07-07 | 2016-07-07 | Vaccine against rsv |
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Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9630994B2 (en) | 2014-11-03 | 2017-04-25 | University Of Washington | Polypeptides for use in self-assembling protein nanostructures |
WO2017005844A1 (en) | 2015-07-07 | 2017-01-12 | Janssen Vaccines & Prevention B.V. | Vaccine against rsv |
BR112018070323A2 (pt) | 2016-04-05 | 2019-01-29 | Janssen Vaccines & Prevention Bv | vacina contra rsv |
WO2017207480A1 (en) | 2016-05-30 | 2017-12-07 | Janssen Vaccines & Prevention B.V. | Stabilized pre-fusion rsv f proteins |
TWI761453B (zh) * | 2017-03-01 | 2022-04-21 | 英商梅迪繆思有限公司 | 抗rsv單株抗體配製物 |
BR112019020661A2 (pt) | 2017-04-04 | 2020-05-05 | University Of Washington | nanoestruturas de proteína de auto-montagem que exibem proteínas f de paramixovírus e/ou pneumovírus e seu uso |
EP3624844A1 (en) * | 2017-05-17 | 2020-03-25 | Janssen Vaccines & Prevention B.V. | Methods and compositions for inducing protective immunity against rsv infection |
AU2019228551A1 (en) | 2018-02-28 | 2020-10-15 | University Of Washington | Self-assembling nanostructure vaccines |
EP3880243A1 (en) | 2018-11-13 | 2021-09-22 | Janssen Vaccines & Prevention B.V. | Stabilized pre-fusion rsv f proteins |
CN115038461A (zh) | 2020-01-16 | 2022-09-09 | 杨森制药公司 | FimH突变体、其组合物及其用途 |
JP2023519740A (ja) | 2020-04-02 | 2023-05-12 | ヤンセン ファッシンズ アンド プリベンション ベーフェー | 安定化型ワクチン組成物 |
WO2022153166A1 (en) | 2021-01-12 | 2022-07-21 | Janssen Pharmaceuticals, Inc. | Fimh mutants, compositions therewith and use thereof |
CN115960214A (zh) * | 2021-10-12 | 2023-04-14 | 中国科学院分子细胞科学卓越创新中心 | 中和呼吸道合胞病毒的全人抗体的设计及应用 |
CN116003536A (zh) * | 2022-09-23 | 2023-04-25 | 暨南大学 | 呼吸道合胞病毒融合前f蛋白突变体及其应用 |
WO2024069420A2 (en) | 2022-09-29 | 2024-04-04 | Pfizer Inc. | Immunogenic compositions comprising an rsv f protein trimer |
WO2024089633A1 (en) | 2022-10-27 | 2024-05-02 | Pfizer Inc. | Rna molecules encoding rsv-f and vaccines containing them |
WO2024089634A1 (en) | 2022-10-27 | 2024-05-02 | Pfizer Inc. | Immunogenic compositions against influenza and rsv |
CN117986382A (zh) * | 2022-11-04 | 2024-05-07 | 北京康乐卫士生物技术股份有限公司 | 针对rsv的重组亚单位疫苗及其应用 |
WO2024127181A1 (en) | 2022-12-11 | 2024-06-20 | Pfizer Inc. | Immunogenic compositions against influenza and rsv |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014160463A1 (en) * | 2013-03-13 | 2014-10-02 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Prefusion rsv f proteins and their use |
Family Cites Families (112)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US17543A (en) * | 1857-06-09 | Improvement in power printing-presses | ||
US4235877A (en) | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
US4372945A (en) | 1979-11-13 | 1983-02-08 | Likhite Vilas V | Antigen compounds |
IL61904A (en) | 1981-01-13 | 1985-07-31 | Yeda Res & Dev | Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same |
EP0173552B1 (en) | 1984-08-24 | 1991-10-09 | The Upjohn Company | Recombinant dna compounds and the expression of polypeptides such as tpa |
US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
NZ230747A (en) | 1988-09-30 | 1992-05-26 | Bror Morein | Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina |
CA2017507C (en) | 1989-05-25 | 1996-11-12 | Gary Van Nest | Adjuvant formulation comprising a submicron oil droplet emulsion |
US5994108A (en) | 1991-11-05 | 1999-11-30 | Board Of Regents, The University Of Texas System | Mutant TAR virus and transdominant tat mutants as pharmacological agents |
FR2705686B1 (fr) | 1993-05-28 | 1995-08-18 | Transgene Sa | Nouveaux adénovirus défectifs et lignées de complémentation correspondantes. |
US5851806A (en) | 1994-06-10 | 1998-12-22 | Genvec, Inc. | Complementary adenoviral systems and cell lines |
DE69535178T2 (de) | 1994-06-10 | 2006-12-14 | Genvec, Inc. | Adenoviren-vektor systeme und zelllinien |
US5965541A (en) | 1995-11-28 | 1999-10-12 | Genvec, Inc. | Vectors and methods for gene transfer to cells |
US5846782A (en) | 1995-11-28 | 1998-12-08 | Genvec, Inc. | Targeting adenovirus with use of constrained peptide motifs |
US5559099A (en) | 1994-09-08 | 1996-09-24 | Genvec, Inc. | Penton base protein and methods of using same |
US5786464C1 (en) | 1994-09-19 | 2012-04-24 | Gen Hospital Corp | Overexpression of mammalian and viral proteins |
AUPM873294A0 (en) | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
US5837520A (en) | 1995-03-07 | 1998-11-17 | Canji, Inc. | Method of purification of viral vectors |
ES2333425T5 (es) | 1995-06-15 | 2012-08-28 | Crucell Holland B.V. | Sistemas de empaquetado para adenovirus recombinante humano destinados a terapia génica |
US5837511A (en) | 1995-10-02 | 1998-11-17 | Cornell Research Foundation, Inc. | Non-group C adenoviral vectors |
CA2177085C (en) | 1996-04-26 | 2007-08-14 | National Research Council Of Canada | Adenovirus e1-complementing cell lines |
IL127692A0 (en) | 1996-07-01 | 1999-10-28 | Rhone Poulenc Rorer Sa | Method for producing recombinant adenovirus |
FR2751343B1 (fr) | 1996-07-16 | 1998-12-18 | Transgene Sa | Procede de conservation de virus recombinants infectieux, suspension aqueuse virale et utilisation comme medicament |
WO1998010087A1 (en) | 1996-09-06 | 1998-03-12 | Trustees Of The University Of Pennsylvania | Chimpanzee adenovirus vectors |
KR100503701B1 (ko) | 1996-11-20 | 2005-07-26 | 인트로겐 테라페티스, 인코퍼레이티드 | 아데노바이러스 벡터를 생산하고 정제하는 개선된 방법 |
US7732129B1 (en) | 1998-12-01 | 2010-06-08 | Crucell Holland B.V. | Method for the production and purification of adenoviral vectors |
US6261823B1 (en) | 1996-12-13 | 2001-07-17 | Schering Corporation | Methods for purifying viruses |
US5851808A (en) | 1997-02-28 | 1998-12-22 | Baylor College Of Medicine | Rapid subcloning using site-specific recombination |
CA2283253A1 (en) | 1997-03-04 | 1998-09-11 | Baxter International Inc. | Adenovirus e1-complementing cell lines |
US6020191A (en) | 1997-04-14 | 2000-02-01 | Genzyme Corporation | Adenoviral vectors capable of facilitating increased persistence of transgene expression |
US6210683B1 (en) | 1997-09-05 | 2001-04-03 | Merck & Co., Inc. | Stabilizers containing recombinant human serum albumin for live virus vaccines |
BR9908015A (pt) | 1998-02-17 | 2001-04-24 | Schering Corp | Composições que compreendem vìrus e métodos para concentração de preparações de vìrus |
US5981225A (en) | 1998-04-16 | 1999-11-09 | Baylor College Of Medicine | Gene transfer vector, recombinant adenovirus particles containing the same, method for producing the same and method of use of the same |
US6113913A (en) | 1998-06-26 | 2000-09-05 | Genvec, Inc. | Recombinant adenovirus |
EP1133316B1 (en) | 1998-11-16 | 2009-01-21 | Introgen Therapeutics, Inc. | Formulation of adenovirus for gene therapy |
US6225289B1 (en) | 1998-12-10 | 2001-05-01 | Genvec, Inc. | Methods and compositions for preserving adenoviral vectors |
EP1816205B1 (en) | 1999-05-17 | 2011-08-10 | Crucell Holland B.V. | Recombinant Adenovirus based on serotype 48 (Ad48). |
US6913922B1 (en) | 1999-05-18 | 2005-07-05 | Crucell Holland B.V. | Serotype of adenovirus and uses thereof |
US6492169B1 (en) | 1999-05-18 | 2002-12-10 | Crucell Holland, B.V. | Complementing cell lines |
US6281823B1 (en) | 1999-09-21 | 2001-08-28 | Agere Systems Guardian Corp. | Direct digital synthesis using a sine weighted DAC |
DE19955558C2 (de) | 1999-11-18 | 2003-03-20 | Stefan Kochanek | Permanente Amniozyten-Zelllinie, ihre Herstellung und Verwendung zur Herstellung von Gentransfervektoren |
AU4346101A (en) | 2000-03-07 | 2001-09-17 | Merck & Co., Inc. | Adenovirus formulations |
NZ523036A (en) | 2000-05-08 | 2004-04-30 | Davisco Foods Internat Inc | Enzymatic treatment of whey proteins for the production of antihypertensive peptides, the resulting products and treatment of hypertension in mammals |
AUPR878401A0 (en) * | 2001-11-09 | 2001-12-06 | Biota Holdings Ltd | Methods for identifying or screening anti-viral agents |
EP1453536A4 (en) | 2001-12-12 | 2009-08-26 | Mayne Pharma Int Pty Ltd | COMPOSITION FOR PRESERVING VIRUSES |
US20030232018A1 (en) | 2002-01-18 | 2003-12-18 | Berlex Biosciences | Stabilized formulations of adenovirus |
US20030180936A1 (en) | 2002-03-15 | 2003-09-25 | Memarzadeh Bahram Eric | Method for the purification, production and formulation of oncolytic adenoviruses |
SI1497438T1 (sl) | 2002-04-25 | 2010-03-31 | Crucell Holland Bv | Sredstva in postopki za pripravo adenovirusnih vektorjev |
ES2310247T3 (es) | 2002-04-25 | 2009-01-01 | Crucell Holland B.V. | Vectores adenovirales estables y metodos de propagacion de los mismos. |
ES2357366T3 (es) | 2002-05-14 | 2011-04-25 | MERCK SHARP & DOHME CORP. | Procedimientos de purificación de adenovirus. |
SE0202110D0 (sv) | 2002-07-05 | 2002-07-05 | Isconova Ab | Iscom preparation and use thereof |
AU2003268210A1 (en) | 2002-08-28 | 2004-03-19 | Introgen Therapeutics Inc. | Chromatographic methods for adenovirus purification |
SE0301998D0 (sv) | 2003-07-07 | 2003-07-07 | Isconova Ab | Quil A fraction with low toxicity and use thereof |
CA2553541C (en) | 2004-01-23 | 2015-04-21 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Chimpanzee adenovirus vaccine carriers |
AU2005214090B2 (en) | 2004-02-23 | 2008-09-11 | Crucell Holland B.V. | Virus purification methods |
CN101155915B (zh) | 2005-04-11 | 2013-12-04 | 克鲁塞尔荷兰公司 | 利用超滤进行病毒纯化 |
WO2007104792A2 (en) | 2006-03-16 | 2007-09-20 | Crucell Holland B.V. | Recombinant adenoviruses based on serotype 26 and 48, and use thereof |
WO2007110409A1 (en) | 2006-03-27 | 2007-10-04 | Crucell Holland B.V. | Compositions comprising a recombinant adenovirus and an adjuvant |
EP2099486A2 (en) | 2006-11-30 | 2009-09-16 | Government Of The United States Of America, As Represented by the Secretary | Codon modified immunogenic compositions and methods of use |
US7901388B2 (en) | 2007-07-13 | 2011-03-08 | Bacoustics, Llc | Method of treating wounds by creating a therapeutic solution with ultrasonic waves |
AU2008340949A1 (en) | 2007-12-24 | 2009-07-02 | Glaxosmithkline Biologicals S.A. | Recombinant RSV antigens |
EP2257809B1 (en) | 2008-02-29 | 2012-02-08 | Tibotec Pharmaceuticals | Method for identifying inhibitors against viruses that use a class i fusion protein |
US8225289B2 (en) | 2008-03-04 | 2012-07-17 | Wind River Systems, Inc. | Method and system for improved tool interaction with a target |
ES2532015T3 (es) | 2008-11-03 | 2015-03-23 | Crucell Holland B.V. | Método para la producción de vectores adenovíricos |
EP3718566B1 (en) | 2008-12-09 | 2024-06-12 | Novavax, Inc. | Modified rsv f proteins and methods of their use |
CN101464897A (zh) | 2009-01-12 | 2009-06-24 | 阿里巴巴集团控股有限公司 | 一种词匹配及信息查询方法及装置 |
KR101763093B1 (ko) | 2009-02-02 | 2017-07-28 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 시미안 아데노바이러스 핵산- 및 아미노산-서열, 이를 포함하는 벡터 및 이의 용도 |
US9492531B2 (en) | 2009-06-24 | 2016-11-15 | Glaxosmithkline Biologicals Sa | Recombinant RSV vaccines |
MX2012000036A (es) | 2009-06-24 | 2012-02-28 | Glaxosmithkline Biolog Sa | Vacuna. |
DK3178490T3 (da) | 2009-07-15 | 2022-06-20 | Glaxosmithkline Biologicals Sa | RSV F-proteinsammensætninger og fremgangsmåder til fremstilling af disse |
WO2011020079A1 (en) | 2009-08-13 | 2011-02-17 | Calmune Corporation | Antibodies against human respiratory syncytial virus (rsv) and methods of use |
CN102575233B (zh) | 2009-10-15 | 2014-07-16 | 克鲁塞尔荷兰公司 | 从高细胞密度培养物纯化腺病毒的方法 |
AU2010305765B2 (en) | 2009-10-15 | 2015-07-02 | Crucell Holland B.V. | Method for the purification of adenovirus particles |
WO2011050168A2 (en) | 2009-10-21 | 2011-04-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Servic | Rsv immunogens, antibodies and compositions thereof |
EA201290772A1 (ru) | 2010-02-12 | 2013-02-28 | КРКА, д.д., НОВО МЕСТО | Новые формы ивабрадина гидрохлорида |
WO2011098592A1 (en) | 2010-02-15 | 2011-08-18 | Crucell Holland B.V. | Method for the production of ad26 adenoviral vectors |
US8772258B2 (en) | 2010-07-02 | 2014-07-08 | Ensysce Biosciences, Inc. | Single walled carbon nanotube/sirna complexes and methods related thereto |
CA3062786C (en) | 2010-07-09 | 2022-04-19 | Janssen Vaccines & Prevention B.V. | Anti-human respiratory syncytial virus (rsv) antibodies and methods of use |
US8317672B2 (en) | 2010-11-19 | 2012-11-27 | Kensey Nash Corporation | Centrifuge method and apparatus |
PT2707385T (pt) | 2011-05-13 | 2017-12-19 | Glaxosmithkline Biologicals Sa | Antigénios de f de rsv pré-fusão |
CN104379733B (zh) | 2012-03-12 | 2016-01-20 | 克鲁塞尔荷兰公司 | 具改变末端的重组腺病毒群 |
US8932607B2 (en) | 2012-03-12 | 2015-01-13 | Crucell Holland B.V. | Batches of recombinant adenovirus with altered terminal ends |
ES2605946T3 (es) | 2012-03-14 | 2017-03-17 | Bayer Intellectual Property Gmbh | Imidazopiridazinas sustituidas |
MY169352A (en) | 2012-03-22 | 2019-03-25 | Janssen Vaccines & Prevention Bv | Vaccine against rsv |
WO2014005643A1 (en) | 2012-07-05 | 2014-01-09 | Okairos Ag | Novel prime-boosting regimens involving immunogenic polypeptides encoded by polynucleotides |
JP6210998B2 (ja) | 2012-11-15 | 2017-10-11 | 一般財団法人化学及血清療法研究所 | ベクターワクチンおよび生ワクチンの併用による感染症の予防方法 |
US9738689B2 (en) * | 2013-03-13 | 2017-08-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Prefusion RSV F proteins and their use |
WO2014153160A2 (en) | 2013-03-14 | 2014-09-25 | Peroxyium, Inc., Delaware C Corp. | METHOD OF ENHANCING THE BIODISTRIBUTION AND TISSUE TARGETING PROPERTIES OF THERAPEUTIC CeO2 PARTICLES VIA NANO-ENCAPSULATION AND COATING |
EA035846B1 (ru) | 2013-04-15 | 2020-08-20 | Янссен Вэксинс Энд Превеншн Б.В. | Антитела человека, связывающиеся с g-белком rsv |
US10196438B2 (en) | 2013-04-15 | 2019-02-05 | Janssen Vaccines & Prevention B.V. | Human antibodies binding to RSV G protein |
MX361774B (es) | 2013-04-25 | 2018-12-17 | Janssen Vaccines & Prevention Bv | Polipéptidos f de prefusión del virus sincicial respiratorio (rsv) solubles y estabilizados. |
PE20160045A1 (es) | 2013-06-17 | 2016-02-18 | Crucell Holland Bv | Polipeptidos f de prefusion del virus sincicial respiratorio (rsv) solubles y estabilizados |
WO2015013551A1 (en) | 2013-07-25 | 2015-01-29 | Marshall Christopher Patrick | Conformationally stabilized rsv pre-fusion f proteins |
PL3046536T3 (pl) | 2013-09-19 | 2019-06-28 | Janssen Vaccines & Prevention B.V. | Ulepszone formulacje adenowirusów |
JP6664338B2 (ja) | 2014-06-13 | 2020-03-13 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 免疫原性組合せ物 |
JP6350376B2 (ja) | 2015-04-23 | 2018-07-04 | 住友金属鉱山株式会社 | 非水系電解質二次電池用正極活物質及びその製造方法、並びにその正極活物質を用いた非水系電解質二次電池 |
JP6840718B2 (ja) * | 2015-07-07 | 2021-03-10 | ヤンセン ファッシンズ アンド プリベンション ベーフェーJanssen Vaccines & Prevention B.V. | 安定化された可溶性融合前rsv fポリペプチド |
WO2017005844A1 (en) | 2015-07-07 | 2017-01-12 | Janssen Vaccines & Prevention B.V. | Vaccine against rsv |
BR112018070323A2 (pt) | 2016-04-05 | 2019-01-29 | Janssen Vaccines & Prevention Bv | vacina contra rsv |
AU2017248021B2 (en) | 2016-04-05 | 2021-08-12 | Janssen Vaccines & Prevention B.V. | Stabilized soluble pre-fusion RSV F proteins |
WO2017207480A1 (en) | 2016-05-30 | 2017-12-07 | Janssen Vaccines & Prevention B.V. | Stabilized pre-fusion rsv f proteins |
US10522129B2 (en) | 2016-10-06 | 2019-12-31 | Gopro, Inc. | Active acoustic and vibration noise canceling in waterproof camera |
KR20180056310A (ko) | 2016-11-18 | 2018-05-28 | 삼성전자주식회사 | 복합양극활물질, 이를 채용한 양극과 리튬전지 및 그 제조방법 |
EP3624844A1 (en) | 2017-05-17 | 2020-03-25 | Janssen Vaccines & Prevention B.V. | Methods and compositions for inducing protective immunity against rsv infection |
EP3681533A1 (en) | 2017-09-15 | 2020-07-22 | Janssen Vaccines & Prevention B.V. | Method for the safe induction of immunity against rsv |
EP3880243A1 (en) | 2018-11-13 | 2021-09-22 | Janssen Vaccines & Prevention B.V. | Stabilized pre-fusion rsv f proteins |
MX2021012991A (es) | 2019-04-25 | 2021-12-10 | Janssen Vaccines & Prevention Bv | Antigenos de gripe recombinantes. |
CA3140234A1 (en) | 2019-05-15 | 2020-11-19 | Janssen Vaccines & Prevention B.V. | Prophylactic treatment of respiratory syncytial virus infection with an adenovirus based vaccine |
US20220273787A1 (en) | 2019-05-15 | 2022-09-01 | Janssen Vaccines & Prevention B.V. | Co-administration of seasonal influenza vaccine and an adenovirus based respiratory syncytial virus vaccine |
JP2023519740A (ja) | 2020-04-02 | 2023-05-12 | ヤンセン ファッシンズ アンド プリベンション ベーフェー | 安定化型ワクチン組成物 |
CA3188170A1 (en) | 2020-06-29 | 2022-01-06 | Janssen Vaccines & Prevention B.V. | Vaccine combination against respiratory syncytial virus infection |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014160463A1 (en) * | 2013-03-13 | 2014-10-02 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Prefusion rsv f proteins and their use |
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