JP5922573B2 - ブドウ球菌クランピング因子aの変異体を含む免疫原性組成物 - Google Patents
ブドウ球菌クランピング因子aの変異体を含む免疫原性組成物 Download PDFInfo
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- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
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Description
本発明のさらなる態様は、本発明のポリペプチド、断片または融合タンパク質をコードするポリヌクレオチドを提供する。
(a)配列番号2のポリヌクレオチド配列の全長にわたって、配列番号2の全ての配列と少なくとも85%の同一性、好ましくは、少なくとも90%の同一性、より好ましくは、少なくとも95%の同一性、さらにより好ましくは、少なくとも97、98もしくは99%または正確な同一性を有するポリヌクレオチド配列;または、
(b)配列番号4〜44のアミノ酸配列の全長にわたって、配列番号4〜44から選択される任意のアミノ酸配列と少なくとも85%の同一性、好ましくは、少なくとも90%の同一性、より好ましくは、少なくとも95%の同一性、さらにより好ましくは、少なくとも97、98もしくは99%または100%正確な同一性を有するポリペプチドをコードするポリヌクレオチド配列;
を含む、またはそれらからなる単離したポリヌクレオチドを提供する。
アルゴリズム:Needleman and Wunsch,J.Mol Biol.48:443−453(1970)
比較行列:HenikoffおよびHenikoff, Proc. Natl. Acad.Sci. USA.89:10915−10919(1992)のBLOSSUM62
ギャップペナルティ:8
ギャップ長ペナルティ:2
これらのパラメータを用いるのに有用なプログラムは、ウィスコンシン州マディソンにあるGenetics Computer Groupの「gap」プログラムとして公的に入手可能である。前述のパラメータは、ペプチド比較のデフォルトパラメータである(末端ギャップに対するペナルティはなし)。
アルゴリズム:Needleman and Wunsch, J. Mol. Biol. 48:443−453(1970)
比較行列:整合=+10、不整合=0
ギャップペナルティ:50
ギャップ長ペナルティ:3
ウィスコンシン州マディソンにあるGenetics Computer Groupの「gap」プログラムとして入手可能である。これらは、核酸比較のデフォルトパラメータである。
本発明は、本発明の1つまたは複数のポリヌクレオチドを含むベクター、本発明のベクターで遺伝子操作した宿主細胞、および組換え技術による本発明のポリペプチドの産生にも関する。無細胞翻訳系を用いて、本発明のDNAコンストラクト由来のRNAを用いてかかるタンパク質を産生することもできる。
本発明のさらなる態様は、組み合わせた時、ブドウ球菌感染に対する効果的な免疫原性組成物をもたらすブドウ球菌抗原の特定の組み合わせを開示する。この免疫原性組成物の有効性は、主に、黄色ブドウ球菌に対する防御反応を引き起こすその能力によって決定されるが、それらの免疫原性組成物は、表皮ブドウ球菌などの関連細菌に対する防御効果も生じさせることが好ましい。
グループa)細胞外成分結合タンパク質;
グループb)トランスポータータンパク質;
グループc)毒素または病原性調節因子
グループd)構造タンパク質
から選択される2、3または4つの異なるグループから選択される2、3、4、5または6以上のいくつかのタンパク質を含む。
グループa)ラミニン受容体、SitC/MntC/唾液結合タンパク質、EbhA、EbhB、エラスチン結合タンパク質(EbpS)、EFB(FIB)、SBI、ClfA、SdrC、SdrD、SdrE、SdrG、SdrH、SasF、リパーゼGehD、SasA、SasB、SasC、SasD、SasK、FnbA、FnbB、Cna、ClfB、FbpA、Npase、IsaA/PisA、SsaA、EPB、SSP−1、SSP−2、HBP、ビトロネクチン結合タンパク質、フィブリノゲン結合タンパク質、コアグラーゼ、FigおよびMAPからなる群から選択される少なくとも1つのブドウ球菌細胞外成分結合タンパク質またはその断片;
グループb)免疫優性ABCトランスポーター、IsdA、IsdB、IsdC、Mg2+トランスポーター、HarA、SitCおよびNi ABCトランスポーターからなる群から選択される少なくとも1つのブドウ球菌トランスポータータンパク質またはその断片;
グループc)EsxA、EsxB、RNA III活性化タンパク質(RAP)からなる群から選択される少なくとも1つのブドウ球菌の病原性調節因子、毒素またはその断片;
グループd)MRPIIおよび自己溶菌酵素からなる群から選択される少なくとも1つのブドウ球菌構造タンパク質またはその免疫原性断片。
一実施形態において、本発明の免疫原性組成物は、ブドウ球菌の糖抗原および変異ClfAポリペプチドを含む。例えば、この免疫原性組成物は、任意に担体タンパク質に結合している黄色ブドウ球菌の5型および/または8型の莢膜糖類を含む。
PNAGは多糖細胞間アドヘシンであり、任意に、N−アセチルおよび/またはO−スクシニル構成要素で置換されたβ−(1→6)結合グルコサミンのポリマーで構成されている。この多糖は黄色ブドウ球菌および表皮ブドウ球菌の両方に存在し、いずれかの供給源から単離することができる(Joyce et al 2003, Carbohydrate Research 338;903;Maira−Litran et al 2002,Infect.Imun.70;4433)。例えば、PNAGは、黄色ブドウ球菌株MN8mから単離することができる(WO04/43407)。dPNAGの調製については、WO04/43405に記載されている。
ヒトに感染を引き起こす黄色ブドウ球菌のほとんどの株は、5型多糖または8型多糖のいずれか一方を含む。ヒト株の約60%が8型であり、約30%が5型である。5型および8型の莢膜多糖抗原の構造については、Moreau et al Carbohydrate Res. 201;285(1990)およびFournier et al Infect. Immun. 45;87(1984)に記載されている。両方ともそれらの反復単位中にFucNAcpおよびManNAcAを有し、ManNAcAはスルフヒドリル基を導入するために用いることができる。
5型
→4)−β−D−ManNAcA−(1→4)−α−L−FucNAc(3OAc)−(1→3)−β−D−FucNAc−(1→
8型
→3)−β−D−ManNAcA(4OAc)−(1→3)−α−L−FucNAc(1→3)−α−D−FucNAc(1→
多糖は、例えば、米国特許第6294177号またはInfection and Immunity(1990)58(7);2367に記載の通りに、当該技術者に公知の方法を用いて、黄色ブドウ球菌の適切な株から抽出することができる。例えば、ATCC12902は5型黄色ブドウ球菌株であり、ATCC12605は、8型黄色ブドウ球菌株である。
一実施形態において、本発明の免疫原性組成物は、米国特許第6294177号に記載の黄色ブドウ球菌336抗原を含む。
表皮ブドウ球菌のATCC−31432株、SE−360株およびSE−10株は、それぞれ、I型、II型およびIII型の3つの異なる莢膜型の特徴を示す(Ichiman and Yoshida 1981, J. Appl. Bacteriol. 51;229)。表皮ブドウ球菌の各血清型から抽出された莢膜多糖は、I型、II型およびIII型の多糖を構成する。多糖類は、米国特許第4197290号に記載の方法またはIchiman et al 1991, J. Appl. Bacteriol. 71;176に記載の方法を含むいくつかの方法によって抽出され得る。
ワクチン接種における多糖類の使用に関連する問題の中に、多糖類それ自体が弱い免疫原であるという事実がある。この免疫原性の欠如を克服するように設計されている戦略には、バイスタンダーT細胞ヘルプ(bystander T−cell help)を提供する巨大タンパク質担体への多糖の結合が含まれる。一実施形態において、本明細書で利用する多糖を、バイスタンダーT細胞ヘルプを提供するタンパク質担体に結合させる。多糖またはオリゴ糖の免疫原と結合させるのに用いられ得るこれらの担体の例として、ジフテリアおよび破傷風トキソイド(DT、DT Crm197およびTT)、キーホールリンペットヘモシアニン(KLH)、緑膿菌エキソプロテインA(rEPA)およびツベルクリンの精製タンパク質誘導体(PPD)、インフルエンザ菌のプロテインD、ニューモリシンまたは上記のいずれかの断片が挙げられる。使用に適する断片には、ヘルパーTエピトープを包含する断片が含まれる。特に、プロテインD断片は、任意に、このタンパク質のN末端の1/3を含む。プロテインDは、インフルエンザ菌のIgD結合タンパク質である(EP0 594 610 B1)。
本発明は、本発明のClfAのポリペプチド、断片または融合タンパク質および医薬的に許容される賦形剤を含む免疫原性組成物またはワクチンを提供する。
OM174(2−デオキシ−6−o−[2−デオキシ−2−[(R)−3−ドデカノイルオキシテトラ−デカノイルアミノ]−4−o−ホスホノ−β−D−グルコピラノシル]−2−[(R)−3−ヒドロキシテトラデカノイルアミノ]−α−D−グルコピラノシルジハイドロジェンホスフェート)、(WO95/14026)
OM294DP(3S,9R)−3−[(R)−ドデカノイルオキシテトラデカノイルアミノ]−4−オキソ−5−アザ−9(R)−[(R)−3−ヒドロキシテトラデカノイルアミノ]デカン−1,10−ジオール,1,10−ビス(ジハイドロジェンホスフェート)、(WO99/64301およびWO00/0462)
OM197MP−AcDP(3S−,9R)−3−[(R)−ドデカノイルオキシテトラデカノイルアミノ]−4−オキソ−5−アザ−9−[(R)−3−ヒドロキシテトラデカノイルアミノ]デカン−1,10−ジオール,1−ジハイドロジェンホスフェート10−(6−アミノヘキサノエート)、(WO01/46127)。
B2312:
黄色ブドウ球菌NCTC8325株由来の40〜559番目のアミノ酸をコードするclfA遺伝子断片のコドンを最適化し、GeneArt(レーゲンスブルク、ドイツ)によって2つの部分に合成した。この遺伝子断片は、N1、N2およびN3と同定された3つの構造ドメインをコードし、ClfAのフィブリノゲン結合活性を含む。ライゲーションができるようにするために、制限酵素部位のNdeIおよびSacIIを第一の合成遺伝子部分の末端に加え、SacIIおよびXhoIを第2の合成遺伝子部分に加えた。
BLRは、プラスミドモノマーの収率を改善するBL21のrecA−誘導体であり、反復配列を含む標的プラスミドを安定化するのを助けることができるか、またはその生成物はDE3プロファージの減少をもたらすことができる。この株はテトラサイクリン耐性(12.5μg/ml)である。
鋳型として(mut474を有する)N123変異を含む発現ベクターを用いる部位特異的変異誘発(Quickchange Site−directed Mutagenesis Kit;Stratagene)により、N123ドメインの野生型配列(474番目に変異がない40〜559番目のアミノ酸)を修復した。標準手順に従って、N123ドメイン(野生型配列)を含む発現ベクターで大腸菌BLR(DE3)株を形質転換することにより、最終株が作られた。
pET−ClfAコンストラクトで形質転換した大腸菌を、培養槽(ClfA−N1N2N3 H474)または振盪フラスコ(ClfA−N1N2N3野生型)のいずれか一方で培養し、IPTGを用いて発現を誘導した。大腸菌細胞ペーストを収集し、50mM NaCl、2mM EDTAおよび1mM PMSFを含む50mMリン酸緩衝液pH7.2に懸濁し、OD650nmは120に達した。この懸濁液を機械的に破砕し、4℃で30分間、12200gで遠心分離して、上清を含むClfA N1N2N3を生成した。ClfAを、平衡化したSephacryl HR300カラムを用いて上清から精製し、10mM ホウ酸ナトリウム pH9.5で溶出した。ClfAを含む画分を、SDS−PAGEによる純度に基づいて選択し、収集して、0.22μmで滅菌濾過した。
コーティングしたClfAへのフィブリノゲン接着
ClfAタンパク質を、4℃で一晩、リン酸緩衝生理食塩水(PBS)中10μg/mlで高結合マイクロタイタープレート(Nunc Maxisorp)上にコーティングした。これらのプレートを、振盪しながら室温で30分間、PBS−1%BSAでブロッキングした。
ヒトフィブリノゲン(ref:SIGMA F4883−16)を、4℃で一晩、リン酸緩衝生理食塩水(PBS)中10μg/mlで高結合マイクロタイタープレート(Nunc Maxisorp)上にコーティングした。これらのプレートを、振盪しながら室温で30分間、PBS−1%BSAでブロッキングした。
20匹のマウスのグループに、0、14および28日目に、アジュバントAS02Vで製剤化したClfA N123またはClfAの474変異体10μgを筋肉注射により接種した。対照グループにはアジュバントのみを接種した。
20匹のマウスのグループに、0、14および28日目に、アジュバントAS02Vで製剤化したClfAのN123または474変異体10μgを筋肉注射により接種した。対照グループにはアジュバントのみを接種した。
配列番号1 ClfA N1N2N3の核酸
ATG
AGCGAAAACAGCGTGACCCAGAGCGATAGCGCGAGCAACGAAAGCAAAAGCAACGATAGCAGCAGCGTTAGCGC
AGCGCCGAAAACCGATGATACCAACGTGAGCGATACCAAAACCAGCAGCAACACCAACAACGGCGAAACCAGCGTGGCGC
AGAATCCGGCGCAGCAGGAAACCACCCAAAGCTCTAGCACCAACGCGACCACCGAAGAAACCCCGGTGACCGGCGAAGCG
ACCACCACGACGACCAACCAGGCGAATACCCCGGCGACCACCCAGTCTAGCAATACCAATGCGGAAGAACTGGTGAACCA
GACCAGCAACGAAACCACCTCTAATGATACCAACACCGTGAGCAGCGTGAACAGCCCGCAGAACAGCACCAATGCCGAAA
ACGTGAGCACCACCCAGGATACCAGCACCGAAGCGACCCCGAGCAACAACGAAAGCGCACCGCAAAGCACCGATGCGAGC
AACAAAGATGTGGTGAACCAGGCGGTGAATACCAGCGCACCGCGTATGCGTGCGTTTAGCCTGGCCGCGGTTGCGGCGGA
TGCGCCGGTTGCGGGCACCGATATCACCAACCAGCTGACGAACGTGACCGTGGGCATTGATAGCGGCACCACCGTGTATC
CGCATCAGGCGGGCTATGTGAAACTGAACTATGGCTTTAGCGTGCCGAACAGCGCGGTGAAAGGCGATACCTTTAAAATT
ACCGTGCCGAAAGAACTGAACCTGAACGGCGTGACCAGCACCGCGAAAGTGCCGCCGATTATGGCGGGCGATCAGGTGCT
GGCCAACGGCGTGATTGATAGCGATGGCAACGTGATTTATACCTTCACCGATTATGTGAACACCAAAGATGATGTGAAAG
CGACCCTGACCATGCCGGCGTATATTGATCCGGAAAACGTGAAAAAAACCGGCAACGTGACCCTGGCCACCGGCATTGGT
AGCACCACCGCGAACAAAACCGTGCTGGTTGATTATGAAAAATACGGCAAATTCTATAACCTGAGCATCAAAGGCACCAT
TGATCAGATCGATAAAACCAACAACACCTATCGCCAGACCATTTATGTGAATCCGAGCGGCGATAACGTGATTGCGCCGG
TGCTGACCGGCAACCTGAAACCGAACACCGATAGCAACGCGCTGATTGATCAGCAGAACACCAGCATCAAAGTGTACAAA
GTGGATAACGCGGCGGATCTGAGCGAAAGCTATTTTGTGAATCCGGAAAACTTTGAAGATGTGACCAACAGCGTGAACAT
TACCTTTCCGAATCCGAACCAGTATAAAGTGGAATTTAACACCCCGGATGATCAGATTACCACCCCGTATATTGTGGTGG
TGAACGGCCATATTGATCCGAACAGCAAAGGCGATCTGGCCCTGCGTAGCACCCTGTATGGCTATAACAGCAACATTATT
TGGCGTAGCATGAGCTGGGATAACGAAGTGGCGTTTAACAACGGCAGCGGCAGCGGTGATGGCATTGATAAACCGGTGGT
GCCGGAACAGCCGGATGAACCGGGCGAAATTGAACCGATTCCGGAATAA
配列番号2 N1N2N3 ClfA His474の核酸
atgAGCGAAAACAGCGTGACCCAGAGCGATAGCGCGAGCAACGAAAGCAAAAGCAACGATAGCAGCAGCGTTAGCGC
AGCGCCGAAAACCGATGATACCAACGTGAGCGATACCAAAACCAGCAGCAACACCAACAACGGCGAAACCAGCGTGGCGC
AGAATCCGGCGCAGCAGGAAACCACCCAAAGCTCTAGCACCAACGCGACCACCGAAGAAACCCCGGTGACCGGCGAAGCG
ACCACCACGACGACCAACCAGGCGAATACCCCGGCGACCACCCAGTCTAGCAATACCAATGCGGAAGAACTGGTGAACCA
GACCAGCAACGAAACCACCTCTAATGATACCAACACCGTGAGCAGCGTGAACAGCCCGCAGAACAGCACCAATGCCGAAA
ACGTGAGCACCACCCAGGATACCAGCACCGAAGCGACCCCGAGCAACAACGAAAGCGCACCGCAAAGCACCGATGCGAGC
AACAAAGATGTGGTGAACCAGGCGGTGAATACCAGCGCACCGCGTATGCGTGCGTTTAGCCTGGCCGCGGTTGCGGCGGA
TGCGCCGGTTGCGGGCACCGATATCACCAACCAGCTGACGAACGTGACCGTGGGCATTGATAGCGGCACCACCGTGTATC
CGCATCAGGCGGGCTATGTGAAACTGAACTATGGCTTTAGCGTGCCGAACAGCGCGGTGAAAGGCGATACCTTTAAAATT
ACCGTGCCGAAAGAACTGAACCTGAACGGCGTGACCAGCACCGCGAAAGTGCCGCCGATTATGGCGGGCGATCAGGTGCT
GGCCAACGGCGTGATTGATAGCGATGGCAACGTGATTTATACCTTCACCGATTATGTGAACACCAAAGATGATGTGAAAG
CGACCCTGACCATGCCGGCGTATATTGATCCGGAAAACGTGAAAAAAACCGGCAACGTGACCCTGGCCACCGGCATTGGT
AGCACCACCGCGAACAAAACCGTGCTGGTTGATTATGAAAAATACGGCAAATTCTATAACCTGAGCATCAAAGGCACCAT
TGATCAGATCGATAAAACCAACAACACCTATCGCCAGACCATTTATGTGAATCCGAGCGGCGATAACGTGATTGCGCCGG
TGCTGACCGGCAACCTGAAACCGAACACCGATAGCAACGCGCTGATTGATCAGCAGAACACCAGCATCAAAGTGTACAAA
GTGGATAACGCGGCGGATCTGAGCGAAAGCTATTTTGTGAATCCGGAAAACTTTGAAGATGTGACCAACAGCGTGAACAT
TACCTTTCCGAATCCGAACCAGTATAAAGTGGAATTTAACACCCCGGATGATCAGATTACCACCCCGTATATTGTGGTGG
TGAACGGCCATATTGATCCGAACAGCAAAGGCGATCTGGCCCTGCGTAGCACCCTGTATGGCCATAACAGCAACATTATT
TGGCGTAGCATGAGCTGGGATAACGAAGTGGCGTTTAACAACGGCAGCGGCAGCGGTGATGGCATTGATAAACCGGTGGT
GCCGGAACAGCCGGATGAACCGGGCGAAATTGAACCGATTCCGGATAA
配列番号3 黄色ブドウ球菌株NCTC8325のClfA
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPEDSDSDPGSDSGSDSNSDSGSDSGSDSTSDSGSDSASDSDSA
SDSDSASDSDSASDSDSASDSDSDNDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSASDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSESDSDSDSDSDSDSDSDSDSDSDSASDSDSGSD
SDSSSDSDSESDSNSDSESVSNNNVVPPNSPKNGTNASNKNEAKDSKEPLPDTGSEDEAN
TSLIWGLLASIGSLLLFRRKKENKDKK
配列番号4 ClfA N1N2N3のアミノ酸
MSENSVTQSDSASNESKSNDSSSVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTTTTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTSTEATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVTVGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAGDQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTTANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNTDSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPDDQITTPYIVVVNGHIDPNSKGDLALRSTLYGYNSNIIWRSMSWDNEVAFNNGSGSGDGIDKPVVPEQPDEPGEIEPIPE
配列番号5 ClfA N1−3
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号6 ClfA N23
SLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号7 ClfA N23短鎖
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号8 黄色ブドウ球菌株NCTC8325 H474のClfA
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGHNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPEDSDSDPGSDSGSDSNSDSGSDSGSDSTSDSGSDSASDSDSA
SDSDSASDSDSASDSDSASDSDSDNDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSASDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSESDSDSDSDSDSDSDSDSDSDSDSASDSDSGSD
SDSSSDSDSESDSNSDSESVSNNNVVPPNSPKNGTNASNKNEAKDSKEPLPDTGSEDEAN
TSLIWGLLASIGSLLLFRRKKENKDKK
配列番号9 ClfA N1N2N3 H474のアミノ酸
MSENSVTQSDSASNESKSNDSSSVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTTTTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTSTEATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVTVGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAGDQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTTANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNTDSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPDDQITTPYIVVVNGHIDPNSKGDLALRSTLYGHNSNIIWRSMSWDNEVAFNNGSGSGDGIDKPVVPEQPDEPGEIEPIPE
配列番号10 ClfA N1−3 H474
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGHNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号11 ClfA N23 H474
SLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGHNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号12 ClfA N23短鎖 H474
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGHNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号13 黄色ブドウ球菌株NCTC8325のClfA del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPEDSDSDPGSDSGSDSNSDSGSDSGSDSTSDSGSDSASDSDSA
SDSDSASDSDSASDSDSASDSDSDNDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSASDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSESDSDSDSDSDSDSDSDSDSDSDSASDSDSGSD
SDSSSDSDSESDSNSDSESVSNNNVVPPNSPKNGTNASNKNEAKDSKEPLPDTGSEDEAN
TSLIWGLLASIGSLLLFRRKKENKDKK
配列番号14 ClfA N1N2N3 H474 Delのアミノ酸
MSENSVTQSDSASNESKSNDSSSVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTTTTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTSTEATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVTVGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAGDQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTTANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNTDSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPDDQITTPYIVVVNGHIDPNSKGDLALRSTLYGNSNIIWRSMSWDNEVAFNNGSGSGDGIDKPVVPEQPDEPGEIEPIPE
配列番号15 ClfA N1−3 Del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号16 ClfA N23 H474 del
SLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号17 ClfA N23短鎖 del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号18 黄色ブドウ球菌株NCTC8325のClfA del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPEDSDSDPGSDSGSDSNSDSGSDSGSDSTSDSGSDSASDSDSA
SDSDSASDSDSASDSDSASDSDSDNDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSASDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSESDSDSDSDSDSDSDSDSDSDSDSASDSDSGSD
SDSSSDSDSESDSNSDSESVSNNNVVPPNSPKNGTNASNKNEAKDSKEPLPDTGSEDEAN
TSLIWGLLASIGSLLLFRRKKENKDKK
配列番号19 ClfA N1N2N3 del
MSENSVTQSDSASNESKSNDSSSVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTTTTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTSTEATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVTVGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAGDQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTTANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNTDSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPDDQITTPYIVVVNGHIDPNSKGDLALRSTLYNSNIIWRSMSWDNEVAFNNGSGSGDGIDKPVVPEQPDEPGEIEPIPE
配列番号20 ClfA N1−3 del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号21 ClfA N23 del
SLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号22 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号23 黄色ブドウ球菌株NCTC8325のClfA del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPEDSDSDPGSDSGSDSNSDSGSDSGSDSTSDSGSDSASDSDSA
SDSDSASDSDSASDSDSASDSDSDNDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSDSASDSDSDSDSDSD
SDSDSDSDSDSDSDSDSDSDSDSDSDSESDSDSDSDSDSDSDSDSDSDSDSASDSDSGSD
SDSSSDSDSESDSNSDSESVSNNNVVPPNSPKNGTNASNKNEAKDSKEPLPDTGSEDEAN
TSLIWGLLASIGSLLLFRRKKENKDKK
配列番号24 ClfA N1N2N3 del
MSENSVTQSDSASNESKSNDSSSVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTTTTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTSTEATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVTVGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAGDQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTTANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNTDSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPDDQITTPYIVVVNGHIDPNSKGDLALRSTLYSNIIWRSMSWDNEVAFNNGSGSGDGIDKPVVPEQPDEPGEIEPIPE
配列番号25 ClfA N1−3 del
MNMKKKEKHAIRKKSIGVASVLVGTLIGFGLLSSKEADASENSVTQSDSASNESKSNDSS
SVSAAPKTDDTNVSDTKTSSNTNNGETSVAQNPAQQETTQSSSTNATTEETPVTGEATTT
TTNQANTPATTQSSNTNAEELVNQTSNETTSNDTNTVSSVNSPQNSTNAENVSTTQDTST
EATPSNNESAPQSTDASNKDVVNQAVNTSAPRMRAFSLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号26 ClfA N23 del
SLAAVAADAPVAGTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号27 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号28 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号29 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号30 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号31 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号32 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号33 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号34 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号35 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号36 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYGWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号37 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLYIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号38 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTLIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号39 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号40 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号41 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRNSNIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号42 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSTIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号43 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSIIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
配列番号44 ClfA N23短鎖del
GTDITNQLTNVT
VGIDSGTTVYPHQAGYVKLNYGFSVPNSAVKGDTFKITVPKELNLNGVTSTAKVPPIMAG
DQVLANGVIDSDGNVIYTFTDYVNTKDDVKATLTMPAYIDPENVKKTGNVTLATGIGSTT
ANKTVLVDYEKYGKFYNLSIKGTIDQIDKTNNTYRQTIYVNPSGDNVIAPVLTGNLKPNT
DSNALIDQQNTSIKVYKVDNAADLSESYFVNPENFEDVTNSVNITFPNPNQYKVEFNTPD
DQITTPYIVVVNGHIDPNSKGDLALRSIWRSMSWDNEVAFNNGSGSGDGID
KPVVPEQPDEPGEIEPIPE
Claims (16)
- 配列番号4の474番目のアミノ酸のチロシン残基(Y474)が異なるアミノ酸で置換されることによって、Y474の変異を有しない同等のClfAポリペプチドと比較して、フィブリノゲン結合活性が減少するように変異しているClfAポリペプチド。
- 前記異なるアミノ酸が塩基性アミノ酸である、請求項1に記載のClfAポリペプチド。
- 前記異なるアミノ酸がヒスチジンである、請求項1または2に記載のClfAポリペプチド。
- N2ドメインおよびN3ドメインを含むフィブリノゲン結合ドメインを含むClfAポリペプチドの断片であって、配列番号4のY474が異なるアミノ酸で置換されることによって、Y474の変異を有しない同等のClfAポリペプチドと比較して、フィブリノゲン結合活性が減少するように変異している、上記断片。
- 前記異なるアミノ酸が塩基性アミノ酸である、請求項4に記載の断片。
- 前記異なるアミノ酸がヒスチジンである、請求項4または5に記載の断片。
- 配列番号8〜12のいずれか1つのアミノ酸配列からなる、請求項1〜3のいずれか1項に記載のClfAポリペプチドまたは請求項4〜6のいずれか1項に記載の断片。
- 請求項1〜7のいずれか1項に記載のClfAポリペプチドまたは断片を含む融合タンパク質。
- 請求項1〜3のいずれか1項に記載のポリペプチド、請求項4〜7のいずれか1項記載の断片または請求項8に記載の融合タンパク質をコードするポリヌクレオチド。
- 請求項1〜3のいずれか1項に記載のClfAポリペプチドおよび医薬的に許容される賦形剤を含む免疫原性組成物。
- 請求項4〜7のいずれか1項に記載のClfAポリペプチドの断片および医薬的に許容される賦形剤を含む免疫原性組成物。
- 請求項8に記載の融合タンパク質および医薬的に許容される賦形剤を含む免疫原性組成物。
- 請求項1〜8のいずれか1項に記載のClfAポリペプチド、断片または融合タンパク質に、医薬的に許容される賦形剤を添加するステップを含む、請求項10〜12のいずれか1項に記載の免疫原性組成物を作製する方法。
- ブドウ球菌の感染もしくは疾患の治療または予防において使用するための、請求項1〜8のいずれか1項に記載のClfAポリペプチド、断片もしくは融合タンパク質。
- ブドウ球菌の感染もしくは疾患の治療または予防において使用するための、請求項10〜12のいずれか1項に記載の免疫原性組成物。
- ブドウ球菌疾患の治療または予防のための医薬の製造における、請求項1〜8のいずれか1項に記載のClfAポリペプチド、断片もしくは融合タンパク質または請求項10〜12のいずれか1項に記載の免疫原性組成物の使用。
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GBGB0913680.5A GB0913680D0 (en) | 2009-08-05 | 2009-08-05 | Immunogenic composition |
PCT/EP2010/061312 WO2011015590A1 (en) | 2009-08-05 | 2010-08-03 | Immunogenic composition comprising variants of staphylococcal clumping factor a |
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EP (1) | EP2462159A1 (ja) |
JP (1) | JP5922573B2 (ja) |
CA (1) | CA2769748C (ja) |
GB (1) | GB0913680D0 (ja) |
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EP1791560A4 (en) | 2004-09-17 | 2009-01-14 | Merck & Co Inc | POLYPEPTIDES FOR INDUCING AN IMMUNE RESPONSE OF PROTECTION DIRECTED AGAINST STAPHYLOCOCCUS AUREUS |
BRPI0515520A (pt) | 2004-09-22 | 2008-07-29 | Glaxosmithkline Biolog Sa | composição imunogênica, vacina, métodos de preparar uma vacina e de prevenir ou tratar infecção estafilocócica, e, uso de composição imunogênica |
JP2008517900A (ja) | 2004-10-25 | 2008-05-29 | ザ ユニバーシティ オブ ウェスタン オンタリオ | スタフィロコッカス−アウレウスIsdたんぱく質ベースの抗感染薬 |
WO2006121664A2 (en) | 2005-05-05 | 2006-11-16 | Merck & Co., Inc. | Polypeptides for inducing a protective immune response against staphylococcus aureus |
EP2368570A3 (en) | 2006-01-18 | 2012-05-02 | University Of Chicago | Compositions and methods related to staphylococcal bacterium proteins |
US20100021503A1 (en) | 2006-03-30 | 2010-01-28 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
EP2043690A1 (en) | 2006-06-12 | 2009-04-08 | Nabi Biopharmaceuticals | Use of alpha-toxin for treating and preventing staphylococcus infections |
CA2667788A1 (en) | 2006-10-30 | 2008-12-18 | The University Of Western Ontario | Staphylococcus aureus specific anti-infectives |
EP3117832B1 (en) * | 2008-01-31 | 2023-09-27 | The Provost, Fellows, Foundation Scholars, & the other members of Board, of the College of the Holy & Undiv. Trinity of Queen Elizabeth near Dublin | Treatment of microbial infections |
WO2010014304A1 (en) | 2008-07-29 | 2010-02-04 | University Of Chicago | Compositions and methods related to staphylococcal bacterium proteins |
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US8715687B2 (en) | 2014-05-06 |
US20120189650A1 (en) | 2012-07-26 |
GB0913680D0 (en) | 2009-09-16 |
JP2013500733A (ja) | 2013-01-10 |
WO2011015590A1 (en) | 2011-02-10 |
EP2462159A1 (en) | 2012-06-13 |
CA2769748C (en) | 2022-05-17 |
CA2769748A1 (en) | 2011-02-10 |
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