JP2013529065A - 融合タンパク質を含むヒトサイトメガロウイルス(hcmv)による哺乳動物細胞の感染後に放出されるウイルス粒子およびその使用 - Google Patents
融合タンパク質を含むヒトサイトメガロウイルス(hcmv)による哺乳動物細胞の感染後に放出されるウイルス粒子およびその使用 Download PDFInfo
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Abstract
Description
a)粒子が、ウイルス糖タンパク質が包埋されている脂質膜によって包まれ、
b)粒子が、ウイルスDNAまたはキャプシドのいずれも含まず、かつ、
c)粒子が、T細胞抗原pp65の1つ以上の部分と、少なくとも1つの異種ペプチドとを含有する融合タンパク質を含む、
ウイルス粒子ならびにそのようなウイルス粒子または複数のそのようなウイルス粒子の使用に関する。
a)粒子が、ウイルス糖タンパク質が包埋されている脂質膜によって包まれ、
b)粒子が、ウイルスDNAまたはキャプシドのいずれも含まない、
ウイルス粒子である。
a)粒子が、ウイルス糖タンパク質が包埋されている脂質膜によって包まれ、
b)粒子が、ウイルスDNAまたはキャプシドのいずれも含まず、かつ、
c)粒子が、T細胞抗原pp65の1つ以上の部分と少なくとも1つの異種ペプチドとを含有する融合タンパク質を含み、
少なくとも1つの異種ペプチドが、T細胞抗原pp65のアミノ酸配列のアミノ酸位置W175またはA534に挿入されているウイルス粒子によって解決される。
1.細胞
一次ヒト包皮線維芽細胞、CTL株、およびT2細胞を、以前に記述されているように[23]培養した。RMA−S細胞[24]を、10%FCS、2mMのL−グルタミン、50mgゲンタマイシンL−1および5μMのβ−メルカプトエタノールを添加したRPMI−1640培地(PAA Laboratories,Coelbe,Germany)で増殖させた。
ウイルスDNAの突然変異誘発のために、HCMV細菌人工染色体(BAC)pHB5[25]を使用した。pHB5の突然変異誘発を、別のところで記述されているように[21]galK陽性/陰性選択手順[26]に従って実施した。UL83オープンリーディングフレームに挿入したDNA配列は、正確なプロテアソームプロセシングを可能にするため付加的なアミノ酸によって隣接された、HLA−A2提示ペプチドIE1TMY[IE1297−305]をコードした。pp65に融合した付加的なポリペプチドはTSDACMMTMYGGISLLSEFCであり、HLA−A2提示ノナペプチドに下線を付している。BACクローンからのウイルス再構成をHobom et al.[27]に従って実施した。
Irmiere and Gibson[29]によって最初に公表し、以前に記述されているように[20]、グリセロール−酒石酸勾配超遠心分離法によって後期感染HFFからDBを精製した。間接免疫蛍光分析を[30]に記述されているように実施した。モノクローナル抗体65−33(W.Britt,University of Alabama,Birmingham,Alabama,USAの好意により提供された)およびFITC結合二次抗体(DAKO,Hamburg,Germany)を使用してpp65を標識した。核をDAPIで対比染色した。Axiophot−1顕微鏡(Zeiss)を1000倍の倍率で使用して免疫蛍光分析からのデータを収集した。免疫ブロット法のために、タンパク質試料を還元条件下で変性させ、SDS−PAGEによって分離して、400mAで1時間45分間電気ブロッティングすることによってニトロセルロース膜(Millipore,Schwalbach,Germany)に転写した。膜をpp65、β−アクチン(Rockland,Gilbertsville,PA,USA)および糖タンパク質B(gB)に対する抗体[31]と共にインキュベートした。ウエスタンブロットを、ALEXA Fluor 680(Invitrogen,Karlsruhe,Germany)またはIRdye 800(Rockland)に結合した抗マウスまたは抗ウサギ二次抗体でプローブした。ブロットしたタンパク質を検出し、Odyssey赤外画像システム(LI−COR,Lincoln,Nebraska,USA)を用いて定量化した。
酵素結合免疫スポット(Elispot)アッセイを以前に述べられているように[23;32]実施した。HLA−A0201(A2)拘束性HCMV由来ペプチドpp65495−503(pp65NLV−CTL)[33;34]およびIE1297−305(IE1 TMY−CTL)[35]に特異的なCTL株をこれらの分析において使用した。CTL株は、HLA−A2/huCD8二重トランスジェニック(tg)マウスを免疫することによって作製しておいた[23]。
8〜12週齢のHLA−A2トランスジェニックマウス(HHDマウス、[36])を、それぞれRV−HB5(DB−HB5)、RV−SB3(DB−SB3)またはRV−SB6(DB−SB6)のDBを6μg、またはPBSにより腹腔内免疫した。リンパ球を免疫後7日目に脾臓から調製した。CD8T細胞をMACSソーティングによって富化し、IFN−γ分泌細胞の頻度を、ペプチド負荷したRMA−S HHDまたはT2刺激細胞を使用してエクスビボで直接Elispotによって分析した。この設定で、Millipore(Schwalbach/Ts.,Germany)からのElispotプレートを使用した。Elispotアッセイを製造者の推奨に従って実施した。応答細胞の頻度を、Boehm et al[37]によって述べられているように線形回帰分析によって決定した。
この実施例で説明するように、異種ペプチドの挿入部位の選択は細胞質DBの形成のために極めて重要である。
この実施例で示すように、組換えウイルスRV−SB3およびRV−SB6は、pp65発現、ビリオン放出、および粒子へのpp65のパッケージングに関して親株と同等である。
この実施例は、pp65NLVおよびIE1TMYの両方がDB−SB3またはDB−SB6で処理したHFFによって提示されることを示す。
この実施例は、組換えDB(recDB)での免疫が、有意の頻度のIE1TMY特異的CD8T細胞およびpp65NLV特異的CD8T細胞をプライミングすることを示す。
本出願では、以下のように様々な参考文献を引用する。
[1] Mwintshi K, Brennan DC. Prevention and management of cytomegalovirus infection in solid-organ transplantation. Expert Rev Anti Infect Ther 2007; 5(2):295-304.
[2] Rubin RH. The pathogenesis and clinical management of cytomegalovirus infection in the organ transplant recipient: the end of the 'silo hypothesis'. Curr Opin Infect Dis 2007; 20(4):399-407.
[3] Arthurs SK, Eid AJ, Pedersen RA, Dierkhising RA, Kremers WK, Patel R, et al. Delayed-onset primary cytomegalovirus disease after liver transplantation. Liver Transpl 2007; 13(12):1703-9.
[4] Arthurs SK, Eid AJ, Pedersen RA, Kremers WK, Cosio FG, Patel R, et al. Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation. Clin Infect Dis 2008; 46(6):840-6.
[5] Peggs KS. Cytomegalovirus following stem cell transplantation: from pharmacologic to immunologic therapy. Expert Rev Anti Infect Ther 2004; 2(4):559-73.
[6] Hebart H, Einsele H. Clinical aspects of CMV infection after stem cell transplantation. Hum Immunol 2004; 65(5):432-6.
[7] Ljungman P. Risk assessment in haematopoietic stem cell transplantation: viral status. Best Pract Res Clin Haematol 2007; 20(2):209-17.
[8] Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. Biol Blood Marrow Transplant 2003; 9(9):543-58.
[9] Boeckh M, Nichols WG. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004; 103(6):2003-8.
[10] Plotkin SA. Cytomegalovirus vaccines. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5 ed. Elsevier, 2008: p. 1147-54.
[11] Cheeran MC, Lokensgard JR, Schleiss MR. Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev 2009; 22(1):99-126, Table.
[12] Stratton KR, Durch JS, Lawrence R.S. Vaccines for the 21st Century. A Tool for Decisionmaking. Washington, DC: National Academy Press, 2001.
[13] Reddehase MJ, Mutter W, Munch K, Buhring HJ, Koszinowski UH. CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol 1987; 61:3102-8.
[14] Wills MR, Carmichael AJ, Sissons JG. Adaptive Cellular Immunity to Human Cytomegalovirus. In: Reddehase MJ, editor. Cytomegalovirus: Molecular Biology and Immunology. Caister Academic Press, Wymondham, Norfolk, U.K., 2006: p. 341-65.
[15] Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 1995; 333(16):1038-44.
[16] Herr W, Plachter B. Cytomegalovirus and varicella-zoster virus vaccines in hematopoietic stem cell transplantation. Expert Rev Vaccines 2009; 8(8):999-1021.
[17] Schleiss MR. Cytomegalovirus vaccine development. Curr Top Microbiol Immunol 2008; 325:361-82.
[18] Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 2009; 360(12):1191-9.
[19] Bernstein DI, Reap EA, Katen K, Watson A, Smith K, Norberg P, et al. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine 2009; 28(2):484-93.
[20] Pepperl S, Munster J, Mach M, Harris JR, Plachter B. Dense bodies of human cytomegalovirus induce both humoral and cellular immune responses in the absence of viral gene expression. J Virol 2000; 74(13):6132-46.
[21] Mersseman V, Besold K, Reddehase MJ, Wolfrum U, Strand D, Plachter B, et al. Exogenous introduction of an immunodominant peptide from the nonstructural IE1 protein of human cytomegalovirus into the MHC class I presentation pathway by recombinant dense bodies. J Gen Virol 2008; 89(Pt2):369-79.
[22] Mersseman V, Bohm V, Holtappels R, Deegen P, Wolfrum U, Plachter B, et al.
Refinement of strategies for the development of a human cytomegalovirus dense body vaccine. Med Microbiol Immunol 2008; 197(2):97-107.
[23] Besold K, Frankenberg N, Pepperl-Klindworth S, Kuball J, Theobald M, Hahn G, et al. Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2-11-mediated immune evasion. J Gen Virol 2007; 88(Pt 5):1429-39.
[24] Townsend A, Ohlen C, Bastin J, Ljunggren HG, Foster L, Karre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature 1989; 340(6233):443-8.
[25] Borst EM, Hahn G, Koszinowski UH, Messerle M. Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J Virol 1999; 73(10):8320-9.
[26] Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 2005; 33(4):e36.
[27] Hobom U, Brune W, Messerle M, Hahn G, Koszinowski UH. Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes.J Virol 2000; 74(17):7720-9.
[28] Besold K, Wills M, Plachter B. Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition. Virology 2009; 391(1):5-19.
[29] Irmiere A, Gibson W. Isolation and characterization of a noninfectious virionlike particle released from cells infected with human strains of cytomegalovirus. Virology 1983; 130:118-33.
[30] Schmolke S, Drescher P, Jahn G, Plachter B. Nuclear targeting of the tegument protein pp65 (UL83) of human cytomegalovirus: an unusual bipartite nuclear localization signal functions with other portions of the protein to mediate its efficient nuclear transport. J Virol 1995; 69:1071-8.
[31] Utz U, Britt W, Vugler L, Mach M. Identification of a neutralizing epitope on glycoprotein gp58 of human cytomegalovirus. J Virol 1989; 63:1995-2001.
[32] Frankenberg N, Pepperl-Klindworth S, Meyer RG, Plachter B. Identification of a conserved HLA-A2-restricted decapeptide from the IE1 protein (pUL123) of human cytomegalovirus. Virology 2002; 295(2):208-16.
[33] Wills MR, Carmichael AJ, Mynard K, Jin X, Weekes MP, Plachter B, et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65- specific CTL. J Virol 1996; 70:7569-79.
[34] Diamond DJ, York J, Sun JY, Wright CL, Forman SJ. Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood 1997; 90(5):1751-67.
[35] Gallez-Hawkins G, Villacres MC, Li X, Sanborn MC, Lomeli NA, Zaia JA. Use of transgenic HLA A*0201/Kb and HHD II mice to evaluate frequency of cytomegalovirus IE1-derived peptide usage in eliciting human CD8 cytokine response. J Virol 2003; 77(7):4457-62.
[36] Pascolo S, Bervas N, Ure JM, Smith AG, Lemonnier FA, Perarnau B. HLAA2.1- restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 1997; 185(12):2043-51.
[37] Bohm V, Simon CO, Podlech J, Seckert CK, Gendig D, Deegen P, et al. The immune evasion paradox: immunoevasins of murine cytomegalovirus enhance priming of CD8 T cells by preventing negative feedback regulation. J Virol 2008; 82(23):11637-50.
[38] Pepperl-Klindworth S, Plachter B. Current perspectives in vaccine development. In: Reddehase MJ, editor. Cytomegaloviruses: Molecular Biology and Immunology. Caister Academic Press Ltd, Wymondham, Norfolk, U.K., 2006.
Claims (30)
- ヒトサイトメガロウイルス(HCMV)による哺乳動物細胞の感染後に放出されるウイルス粒子であって、
a)該粒子が、ウイルス糖タンパク質が包埋されている脂質膜によって包まれ、
b)該粒子が、ウイルスDNAまたはキャプシドのいずれも含まず、かつ、
c)該粒子が、T細胞抗原pp65の1つ以上の部分と、少なくとも1つの異種ペプチドとを含有する融合タンパク質を含み、
前記少なくとも1つの異種ペプチドが、T細胞抗原pp65のアミノ酸配列のアミノ酸位置W175またはA534に挿入されているウイルス粒子。 - 前記少なくとも1つの異種ペプチドが、T細胞抗原pp65のアミノ酸配列のアミノ酸位置W175に挿入されている、請求項1に記載のウイルス粒子。
- 前記T細胞抗原pp65の前記アミノ酸配列が、配列番号1に従うアミノ酸配列を含む、請求項1または2に記載のウイルス粒子。
- 前記粒子が高度に抗原性である、請求項1〜3のいずれか一項に記載のウイルス粒子。
- 前記粒子が中和抗体の形成を誘導することができる、請求項1〜4のいずれか一項に記載のウイルス粒子。
- 前記粒子がCD8+Tリンパ球応答を誘導することができる、請求項1〜5のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドがMHCクラスI提示抗原である、請求項1〜6のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、pp65とは異なる1つ以上のタンパク質の1つ以上の部分を含む、または、1つ以上の部分から形成される、請求項1〜7のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMV糖タンパク質の1つ以上の部分を含む、または、1つ以上の部分である、請求項1〜8のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMV糖タンパク質gBの1つ以上の部分を含む、または、1つ以上の部分である、請求項1〜9のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMV糖タンパク質gHの1つ以上の部分を含む、または、1つ以上の部分である、請求項1〜9のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、異なるHCMV株からの特定の糖タンパク質の変異体である少なくとも2つのHCMV糖タンパク質を含む、または、前記少なくとも2つのHCMV糖タンパク質から成る、請求項1〜9のいずれか一項に記載のウイルス粒子。
- 前記特定の糖タンパク質の少なくとも2つの変異体の一方が、HCMVのTowne株の変異体であり、前記特定の糖タンパク質の少なくとも2つの変異体の他方が、HCMVのAd169株の変異体である、請求項12に記載のウイルス粒子。
- 前記糖タンパク質が、HCMVのgBタンパク質である、請求項12または13に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMVタンパク質IE1の1つ以上の部分を含む、または、1つ以上の部分である、請求項1〜8のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMV糖タンパク質の1つ以上の部分と、前記HCMVタンパク質IE1の1つ以上の部分とを含む、または、1つ以上の部分である、請求項1〜8のいずれか一項に記載のウイルス粒子。
- 前記少なくとも1つの異種ペプチドが、HCMV以外のヒト病原体の部分であるタンパク質の1つ以上の部分である、請求項1〜8のいずれか一項に記載のウイルス粒子。
- HCMV以外のヒト病原体の部分である前記タンパク質が、HCMV以外の前記ヒト病原体によるヒトの自然感染時に、それに対する細胞傷害性Tリンパ球がヒトにおいて形成されるタンパク質である、請求項17に記載のウイルス粒子。
- HCMV以外の前記ヒト病原体が、HIV−1、HBV、HCVおよびインフルエンザを含む群から選択される前記ヒト病原体である、請求項18に記載のウイルス粒子。
- 前記融合タンパク質が、完全長T細胞抗原pp65と、少なくとも1つの異種ペプチドとを含む前記融合タンパク質である、請求項1〜19のいずれか一項に記載のウイルス粒子。
- 疾患の治療および/または予防のための薬剤を製造するための、請求項1〜20のいずれか一項に記載のウイルス粒子または複数のウイルス粒子。
- 疾患の治療および/または予防のための方法における使用のための、請求項1〜20のいずれか一項に記載のウイルス粒子または複数のウイルス粒子。
- 前記疾患が、前記少なくとも1つの異種ペプチドもしくはその誘導体に対する中和抗体の形成によって、または、前記少なくとも1つの異種ペプチドもしくはその誘導体に対するCD8+Tリンパ球応答の誘導によって治療および/または予防することができる疾患である、請求項21または22に記載のウイルス粒子。
- ワクチンの製造のための、請求項1〜20のいずれか一項に記載のウイルス粒子または複数のウイルス粒子。
- 前記ワクチンが、HCMV感染の治療および/または予防のためである、請求項24に記載のウイルス粒子。
- 前記ワクチンが、移植の副作用の治療および/または予防のためである、請求項24に記載のウイルス粒子。
- 前記移植が、固形臓器または造血幹細胞の移植である、請求項26に記載のウイルス粒子。
- 前記副作用が、HCMV感染によって引き起こされるまたはHCMV感染に付随している、請求項26または27に記載のウイルス粒子。
- 前記疾患または副作用の治療および/または予防のための薬剤を製造するための、請求項1〜20のいずれか一項に記載のウイルス粒子の使用であって、該疾患または副作用が前記請求項のいずれか一項で定義される疾患または副作用である、ウイルス粒子の使用。
- 疾患または副作用の前記治療および/または予防のためのワクチンを製造するための、請求項1〜20のいずれか一項に記載のウイルス粒子の使用であって、該疾患または副作用が前記請求項のいずれか一項で定義される疾患または副作用である、ウイルス粒子の使用。
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US11629172B2 (en) | 2018-12-21 | 2023-04-18 | Pfizer Inc. | Human cytomegalovirus gB polypeptide |
TWI810589B (zh) | 2020-06-21 | 2023-08-01 | 美商輝瑞股份有限公司 | 人巨細胞病毒糖蛋白B(gB)多肽 |
US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002537830A (ja) * | 1999-03-08 | 2002-11-12 | プラハター、ボウド | ヒトサイトメガロウイルス感染後に遊離されるウイルス粒子及び前記粒子のワクチンとしての使用法・用途 |
WO2006004661A1 (en) * | 2004-06-25 | 2006-01-12 | Medimmune Vaccines, Inc. | Recombinant human cytomegalovirus and vaccines comprising heterologous antigens |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5733540A (en) * | 1995-03-08 | 1998-03-31 | Lee; Peter Poon-Hang | Protection from viral infection via colonization of mucosal membranes with genetically modified bacteria |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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WO2006004661A1 (en) * | 2004-06-25 | 2006-01-12 | Medimmune Vaccines, Inc. | Recombinant human cytomegalovirus and vaccines comprising heterologous antigens |
Non-Patent Citations (4)
Title |
---|
JPN6015024015; J. Gen. Virol. Vol.89, Pt. 2, 2008, pp.369-379 * |
JPN6015024016; Med. Microbiol. Immunol. Vol.197, No.2, 2008, pp.97-107 * |
JPN6015024017; Vaccine Vol.25, No.42, 2007, pp.7441-7449 * |
JPN6015024018; J. Virol. Vol.74, No.13, 2000, pp.6132-6146 * |
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