JP2015071598A - 最大限のgag及びnefを樹状細胞に対して標的化することに基づくhivワクチン - Google Patents
最大限のgag及びnefを樹状細胞に対して標的化することに基づくhivワクチン Download PDFInfo
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- JP2015071598A JP2015071598A JP2014205331A JP2014205331A JP2015071598A JP 2015071598 A JP2015071598 A JP 2015071598A JP 2014205331 A JP2014205331 A JP 2014205331A JP 2014205331 A JP2014205331 A JP 2014205331A JP 2015071598 A JP2015071598 A JP 2015071598A
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Abstract
Description
すなわち、本発明は、
(1)抗原提示細胞による抗原提示の有効性を増加させるための方法であって、
1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原に結合して抗体−抗原複合体を形成する樹状細胞(DC)特異的抗体又はその断片を単離及び精製することと、
前記抗体−抗原複合体がプロセシングされT細胞認識のために提示される条件下で前記抗原提示細胞を接触させることと
を含む方法、
(2)抗原提示細胞が樹状細胞を含む、上記(1)に記載の方法、
(3)DC特異的抗体又はその断片が、コヘリン/ドッケリン対の片方に結合する、上記(1)に記載の方法、
(4)DC特異的抗体又はその断片が、コヘリン/ドッケリン対の片方に結合し、改変Gag抗原が、前記コヘリン/ドッケリン対の相補的な片方に結合して複合体を形成する、上記(1)に記載の方法、
(5)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含む、上記(1)に記載の方法、
(6)抗体−抗原複合体が、1又は2以上の新しいグリコシル化部位をさらに含む、上記(1)に記載の方法、
(7)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、前記抗体と前記抗原との間の可動性の増加、前記リンカーのタンパク質分解の減少、及び分泌の増加を提供する1又は2以上のグリコシル化部位を含む、上記(1)に記載の方法、
(8)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含む、上記(1)に記載の方法、
(9)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(1)に記載の方法、
(10)DC特異的抗体又はその断片がヒト化されている、上記(1)に記載の方法、
(11)抗体−抗原複合体が、配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(1)に記載の方法、
(12)DC特異的抗体又はその断片が、MHCクラスI、MHCクラスII、CD1、CD2、CD3、CD4、CD8、CD11b、CD14、CD15、CD16、CD19、CD20、CD29、CD31、CD40、CD43、CD44、CD45、CD54、CD56、CD57、CD58、CD83、CD86、CMRF−44、CMRF−56、DCIR、DC−ASGPR、CLEC−6、CD40、BDCA−2、MARCO、DEC−205、マンノース受容体、ランゲリン、DECTIN−1、B7−1、B7−2、IFN−γ受容体及びIL−2受容体、ICAM−1、Fcγ受容体、LOX−1、並びにASGPRに特異的に結合する抗体から選択される、上記(1)に記載の方法、
(13)抗原提示細胞による抗原提示の有効性を増加させるため方法であって、
抗体−抗原複合体の分泌を増加させる1又は2以上のコドン使用頻度の最適化がなされた改変Nef抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片を単離及び精製することと、
前記抗体−抗原複合体がプロセシングされT細胞認識のために提示される条件下で前記抗原提示細胞を接触させることと
を含む方法、
(14)抗原提示細胞が樹状細胞を含む、上記(13)に記載の方法、
(15)DC特異的抗体又はその断片が、コヘリン/ドッケリン対の片方に結合し、改変Nef抗原が、前記コヘリン/ドッケリン対の相補的な片方に結合して複合体を形成する、上記(13)に記載の方法、
(16)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含む、上記(13)に記載の方法、
(17)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含み、前記リンカーが、前記抗体と前記抗原との間の可動性の増加、前記リンカーのタンパク質分解の減少、及び分泌の増加を提供する1又は2以上のグリコシル化部位を含む、上記(13)に記載の方法、
(18)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含む、上記(13)に記載の方法、
(19)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(13)に記載の方法、
(20)DC特異的抗体又はその断片がヒト化されている、上記(13)に記載の方法、
(21)抗体−抗原複合体が、配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(13)に記載の方法、
(22)DC特異的抗体又はその断片が、MHCクラスI、MHCクラスII、CD1、CD2、CD3、CD4、CD8、CD11b、CD14、CD15、CD16、CD19、CD20、CD29、CD31、CD40、CD43、CD44、CD45、CD54、CD56、CD57、CD58、CD83、CD86、CMRF−44、CMRF−56、DCIR、DC−ASGPR、CLEC−6、CD40、BDCA−2、MARCO、DEC−205、マンノース受容体、ランゲリン、DECTIN−1、B7−1、B7−2、IFN−γ受容体及びIL−2受容体、ICAM−1、Fcγ受容体、LOX−1、並びにASGPRに特異的に結合する抗体から選択される、上記(13)に記載の方法、
(23)1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片を含むワクチン、
(24)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含む、上記(23)に記載のワクチン、
(25)抗体−抗原複合体が、1又は2以上の新しいグリコシル化部位をさらに含む、上記(23)に記載のワクチン、
(26)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、前記抗体と前記抗原との間の可動性の増加、前記リンカーのタンパク質分解の減少、及び分泌の増加を提供する1又は2以上のグリコシル化部位を含む、上記(23)に記載のワクチン、
(27)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含む、上記(23)に記載のワクチン、
(28)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(23)に記載のワクチン、
(29)DC特異的抗体又はその断片がヒト化されている、上記(23)に記載のワクチン、
(30)抗体−抗原複合体が、配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(23)に記載のワクチン、
(31)DC特異的抗体又はその断片が、MHCクラスI、MHCクラスII、CD1、CD2、CD3、CD4、CD8、CD11b、CD14、CD15、CD16、CD19、CD20、CD29、CD31、CD40、CD43、CD44、CD45、CD54、CD56、CD57、CD58、CD83、CD86、CMRF−44、CMRF−56、DCIR、DC−ASGPR、CLEC−6、CD40、BDCA−2、MARCO、DEC−205、マンノース受容体、ランゲリン、DECTIN−1、B7−1、B7−2、IFN−γ受容体及びIL−2受容体、ICAM−1、Fcγ受容体、LOX−1、並びにASGPRに特異的に結合する抗体から選択される、上記(23)に記載のワクチン、
(32)抗体−抗原複合体の分泌を増加させる1又は2以上のコドン使用頻度の最適化がなされた改変Nef抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片を含むワクチン、
(33)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含む、上記(32)に記載のワクチン、
(34)抗体−抗原複合体が、1又は2以上の新しいグリコシル化部位をさらに含む、上記(32)に記載のワクチン、
(35)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含み、前記リンカーが、前記抗体と前記抗原との間の可動性の増加、前記リンカーのタンパク質分解の減少、及び分泌の増加を提供する1又は2以上のグリコシル化部位を含む、上記(32)に記載のワクチン、
(36)抗体−抗原複合体が、DC特異的抗体又はその断片とNef抗原との間に可動性リンカーをさらに含む、上記(32)に記載のワクチン、
(37)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(32)に記載のワクチン、
(38)DC特異的抗体又はその断片がヒト化されている、上記(32)に記載のワクチン、
(39)抗体−抗原複合体が、配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(32)に記載のワクチン、
(40)DC特異的抗体又はその断片が、MHCクラスI、MHCクラスII、CD1、CD2、CD3、CD4、CD8、CD11b、CD14、CD15、CD16、CD19、CD20、CD29、CD31、CD40、CD43、CD44、CD45、CD54、CD56、CD57、CD58、CD83、CD86、CMRF−44、CMRF−56、DCIR、DC−ASGPR、CLEC−6、CD40、BDCA−2、MARCO、DEC−205、マンノース受容体、ランゲリン、DECTIN−1、B7−1、B7−2、IFN−γ受容体及びIL−2受容体、ICAM−1、Fcγ受容体、LOX−1、並びにASGPRに特異的に結合する抗体から選択される、上記(32)に記載のワクチン、
(41)1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片と、抗体−抗原複合体の分泌を増加させる1又は2以上のコドン使用頻度の最適化がなされた改変Nef抗原が結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片とを含むワクチンであって、Gag p17、Gag p24、及びNefに対するHIV特異的T細胞免疫応答を誘導することができるワクチン、
(42)Gag及びNef抗原が融合タンパク質を構成する、上記(41)に記載のワクチン、
(43)Gag及びNef抗原が、1又は2以上の可動性リンカーによって隔てられて融合タンパク質を構成する、上記(41)に記載のワクチン、
(44)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原又はNef抗原との間に可動性リンカーをさらに含む、上記(41)に記載のワクチン、
(45)抗体−抗原複合体が、DC特異的抗体又はその断片とGag抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(41)に記載のワクチン、
(46)DC特異的抗体又はその断片がヒト化されている、上記(41)に記載のワクチン、
(47)配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(41)に記載のワクチン、
(48)1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原が結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片と、
前記DC特異的抗体若しくはその断片又は前記改変Gag抗原に結合して抗体−抗原複合体を形成し、抗体−抗原複合体の分泌を増加させる1又は2以上のコドン使用頻度の最適化がなされた改変Nef抗原
とを含むワクチンであって、Gag p17、Gag p24、及びNefに対するHIV特異的T細胞免疫応答を誘導することができるワクチン、
(49)DC特異的抗体又はその断片Gag及びNef抗原が、融合タンパク質を構成する、上記(48)に記載のワクチン、
(50)Gag及びNef抗原が、1又は2以上の可動性リンカーによって隔てられて融合タンパク質を構成する、上記(48)に記載のワクチン、
(51)タンパク質が、配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される、上記(48)に記載のワクチン、
(52)樹状細胞の有効性を増加させるための方法であって、
患者の樹状細胞を単離することと、
1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片と、
前記DC特異的抗体若しくはその断片又は前記改変Gag抗原に結合して抗体−抗原複合体を形成し、抗体−抗原複合体の分泌を増加させる1又は2以上のコドン使用頻度の最適化がなされた改変Nef抗原とを含む活性化量のワクチンであって、Gag p17、Gag p24、及びNefに対するHIV特異的T細胞免疫応答を誘導することができるワクチンに前記樹状細胞を曝露することと、
前記抗原が負荷され活性化された樹状細胞を、前記患者に再導入することと
を含む方法、
(53)1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっているサイクリンD1又はその断片を含む改変抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片を含むワクチン、
(54)抗体−抗原複合体が、DC特異的抗体又はその断片とサイクリンD1抗原との間に可動性リンカーをさらに含む、上記(53)に記載のワクチン、
(55)抗体−抗原複合体が、1又は2以上の新しいグリコシル化部位をさらに含む、上記(53)に記載のワクチン、
(56)抗体−抗原複合体が、DC特異的抗体又はその断片とサイクリンD1抗原との間に可動性リンカーをさらに含み、前記リンカーが、前記抗体と前記抗原との間の可動性の増加、前記リンカーのタンパク質分解の減少、及び分泌の増加を提供する1又は2以上のグリコシル化部位を含む、上記(53)に記載のワクチン、
(57)抗体−抗原複合体が、DC特異的抗体又はその断片とサイクリンD1抗原との間に可動性リンカーをさらに含み、前記リンカーが、セルロース分解生物に由来するリンカー配列から選択される1又は2以上のグリコシル化部位を含む、上記(53)に記載のワクチン、
(58)DC特異的抗体又はその断片がヒト化されている、上記(53)に記載のワクチン、
(59)DC特異的抗体又はその断片が、コヘリン/ドッケリン対の片方に結合し、改変サイクリンD1抗原が、前記コヘリン/ドッケリン対の相補的な片方に結合して複合体を形成する、上記(53)に記載のワクチン、
(60)樹状細胞の有効性を増加させる方法であって、
患者の樹状細胞を単離することと、
1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっているサイクリンD1又はその断片(複数可)を含む改変抗原に結合して抗体−抗原複合体を形成するDC特異的抗体又はその断片を含む活性化量のワクチンに前記樹状細胞を曝露することと、
前記抗原が負荷され活性化された樹状細胞を前記患者に再導入することと
を含む方法、
(61)配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択されるポリペプチドをコードする単離及び精製された核酸、
(62)配列番号1、2、3、4、5、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、31、又は32から選択される単離及び精製されたポリペプチド、
に、関する。
seqA DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIYYTSILHSGVPS
seqB DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIHYTSILHSGVPS
seqC DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIHYTSILHSGVPS
seqD DIQMTQTTSSLSASLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIHYTSILHSGVPS
seqE DIQMTQTTSSLSTSLGDRVTISCSASQGISNYLNWYQQKPDGTVKLLIHYTSILHSGVPS
************:***********************************:***********
seqA RFSGSGSGTDYSLTIGNLEPEDIATYYCQQFNKLPPTFGGGTKLEIKRTVAAPSVFIFPP
seqB RFSGSGSGTDYSLTISNLEQEDIATYFCQQFNKLPPTFGGGTKLEIKRTVAAPSVFIFPP
seqC RFSGS-SGTDYSLTISNLEQEDIATYFCQQFNKLPPTFGGGTKLEIKRTVAAPSVFIFPP
seqD RFSGSGSGTDYSLTISNLEQEDIATYFCQQFNKPPPTFGGGTKLEIKRTVAAPSVFIFPP
seqE RFSGSGSGTDYSLTISNLEQEDIATYFCQQFNKLPPTFGGGTKLEIKRTVAAPSVFIFPP
***** *********.*** ******:****** **************************
seqA SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
seqB SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
seqC SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
seqD SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
seqE SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
************************************************************
seqA LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
seqB LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
seqC LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
seqD LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
seqE LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
**********************************
(上記はそれぞれ配列番号24、25、26、27、28)
seqA EVKLVESGGGLVQPGGSLKLSCATSGFTFSDYYMYWVRQTPEKRLEWVAYINSGGGSTYY
seqB EVNLVESGGGLVQPGGSLKVSCVTSGFTFSDYYMYWVRQTPEKRLEWVAYINSGGGSTYY
**:****************:**.*************************************
seqA PDTVKGRFTISRDNAKNTLYLQMSRLKSEDTAMYYCARRGLPFHAMDYWGQGTSVTVSSA
seqB PDTVKGRFTISRDNAKNSLYLQMSRLKSEDTAMYYCARRGLPFHAMDYWGQGTLVTVSVA
*****************:*********************************** **** *
seqA KTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
seqB STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
.***********************************************************
seqA LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVF
seqB LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVF
************************************************************
seqA LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
seqB LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
************************************************************
seqA VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
seqB VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
************************************************************
seqA QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
seqB QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
************************************************************
seqA VFSCSVMHEALHNHYTQKSLSLSLGKAS
seqB VFSCSVMHEALHNHYTQKSLSLSLGKAS
****************************
(上記はそれぞれ配列番号29、30)
p17及びnefペプチドエピトープの両方に応答するIFNα産生CD8+T細胞の増殖を刺激した。
gag p24、及びHIV nef内の複数のエピトープを包含する多様なT細胞応答を誘導することができることを実証する。
C515 大腸菌−pET28 [コヘシン−hサイクリンD1−6xHis]
Coh.Cyclin D1を、L培地(Difco社製)中37℃でカナマイシン耐性(40μg/ml)によって選択して増殖させた大腸菌株T7 Express(NEB社製)で発現させ、対数増殖中期まで200回転/分で振とうした。その後、120mg/LのIPTG(Bioline社製)を添加し、さらに3時間後、細胞を遠心分離により回収し、−80℃で保存した。各1Lの発酵に由来する大腸菌細胞を、0.2mlのプロテアーゼ阻害剤カクテルII(Calbiochem社製)を有する50mlの氷冷50mMトリス、1mM EDTA pH8.0に再懸濁した。細胞を、5分間の中止期間をおいて2回氷上で4分間、18の設定で超音波処理(Fisher社製Sonic Dismembrator 60)し、その後17,000r.p.m.、4℃で20分間遠心した(Sorvall社製SA-600)。50mlの細胞溶解産物上清を、10mlのANXセファロースビーズ(GE Healthcare社製)に通し、その後通過画分を、7.5mlの160mMトリス、40mMイミダゾール、4M NaCl pH7.9を有する結合緩衝液に調整して、Ni++で荷電された5mlのHiTrapキレート化HPカラム(GE Healthcare社製)に充填した。結合したタンパク質を、20mM NaPO4、300mM NaCl、10mMイミダゾール pH7.6(緩衝液A)で洗浄し、緩衝液A中10〜500mMのイミダゾール勾配で溶出した。ピーク画分をSDS−PAGEゲルにより分析し、貯溜した。およそ15ミリグラムの貯溜した溶出コヘシン−サイクリンD1融合タンパク質を、10ミリグラムのmPEG-MAL 20k試薬(Nektar社製)と室温で終夜反応させ、それにより20kDaのペグ化基(pegyl group)を遊離システイン残基[それらのいくつかはサイクリンD1ドメイン内にある]に結合させる。この反応の一部をDPBS[Gibco社製]に対して透析し、一部をpH7.5に調整し、その後DTTを室温で1.5時間10mMになるように添加して、あらゆるジスルフィド結合を還元し、その後室温で1.5時間25mMヨードアセトアミドを添加して、遊離システイン残基をアルキル化し、その後20mM DTTを室温で1.5時間添加し、その後DPBSに対して透析した。ペグ化は、タンパク質がDPBSに可溶性であり続けることを保証するために必要であり、アルキル化[インビトロ抗CD40標的化の状況では、タンパク質の活性に必要ではなかった]は、産物に分子間ジスルフィド架橋形態が存在しないことを保証する役目を果たした。
Claims (1)
- 抗原提示細胞による抗原提示の有効性を増加させるための方法であって、
1又は2以上のタンパク質分解部位を除去することによりタンパク質分解されにくくなっている改変Gag抗原に結合して抗体−抗原複合体を形成する樹状細胞(DC)特異的抗体又はその断片を単離及び精製することと、
前記抗体−抗原複合体がプロセシングされT細胞認識のために提示される条件下で前記抗原提示細胞を接触させることと
を含む方法。
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