CN1984666A - 与其他抗病毒剂联合治疗hiv/aids的副痘病毒 - Google Patents
与其他抗病毒剂联合治疗hiv/aids的副痘病毒 Download PDFInfo
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- CN1984666A CN1984666A CNA2005800236070A CN200580023607A CN1984666A CN 1984666 A CN1984666 A CN 1984666A CN A2005800236070 A CNA2005800236070 A CN A2005800236070A CN 200580023607 A CN200580023607 A CN 200580023607A CN 1984666 A CN1984666 A CN 1984666A
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- parapoxvirus
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Abstract
本发明涉及副痘病毒与其他药物联合治疗病毒性疾病,特别是HIV感染和AIDS的用途。本发明还涉及制备基于副痘病毒和其他抗病毒剂组合的药物的方法。特别地,本发明涉及副痘病毒与用于抗逆转录病毒治疗和高活性抗逆转录病毒治疗(HAART)的药物的联合应用。
Description
技术领域
本发明涉及副痘病毒与其他药物联合治疗病毒性疾病,特别是HIV感染和AIDS(艾滋病)的用途。本发明还涉及制备基于副痘病毒和其他抗病毒剂组合的药物的方法。特别地,本发明涉及副痘病毒与用于抗逆转录病毒治疗(ART)和高活性抗逆转录病毒治疗(HAART)的药物的联合应用。
背景技术
PPVO用于治疗病毒感染的应用是已知的[1]。PPVO用于增强免疫系统的应用也是已知的[2]。
HAART是一种已知的用于减少HIV感染的病毒载量(HI病毒载量)的治疗方法。也知道HAART导致患者的CD4+细胞增多[3]。但是,本领域技术人员知道HAART不会导致病毒清除,随着病毒载量降低,感染依然存在。也知道HAART不会引起免疫系统永久性的重建[4]。如果治疗终止或中断,病毒载量将会再次升高,而CD4+细胞数减少[5]。
HAART和细胞因子(如IL-2)的组合增强HAART患者的免疫系统,但不会引起免疫系统永久性的重建而且会发生副作用[6]。
其他类型的治疗(例如再输注自体的、离体扩增的或改良的HIV特异性CTL(细胞毒性T淋巴细胞)克隆)增强CD8+细胞应答。但是这种增强也只是暂时的[7]。免疫缺陷的确切原因和对HIV的免疫保护的关系迄今为止尚未阐明[8]。如果在原发感染的早期阶段通过抗病毒治疗减少HIV病毒载量,则可以建立特异性针对免疫缺陷病毒的有效的免疫[9]。相反,在用HAART治疗的慢性感染患者中不发生HIV特异性免疫应答的增强。而恰恰相反,HIV特异性免疫应答甚至降低[8]。Lu等人的实验表明,免疫调控的缺陷可能存在于免疫应答的诱导阶段,即树突细胞启动病毒特异性应答时[10]。该作者成功地证明了SIV感染的恒河猴在过继转移载有灭活HIV颗粒的自体树突细胞后表现出特异性的细胞和体液免疫应答。
从上述现有技术清楚地看出,迄今为止还没有公开既能够降低慢性感染患者的病毒载量同时又能够引起被感染患者免疫系统永久性重建的治疗方法。
因此,本发明基于提供不仅降低患者病毒载量而且引起免疫系统永久性重建的治疗方法这一技术问题。该治疗方法应当也具有较少的或者没有不希望的副作用。
本发明还基于提供在本发明治疗方法中使用的药物这一技术问题。
附图说明
图1:健康或无免疫应答供体在接受PPVO刺激后CD14高单核细胞的TNF-α产生。每种情况分析了两个供体的全血。(A)健康供体的血液、(B)HIV-感染供体(HIV+)的血液或(C)移植患者(Tx)的血液与葡萄球菌肠毒素B(SEB;2.5μg/ml)、PPVO(6×108个病毒颗粒)、作为PPVO的安慰剂对照的载体、或脂肽(LP1μg/ml)一起温百6小时。然后通过FACS分析确定产TNF-α的CD14高单核细胞的相对量(%)。
图2:PPVO治疗降低了hu-PBL-SCID小鼠的HIV病毒载量。感染HIVBal的hu-PBL-SCID小鼠脾脏中的HIV拷贝数(已对人GAPDHRNA标准化)。示出了每个处理组的平均值±标准误差。PBS(+载体)n=13,AZT(+载体)n=17,PBS+PPVOn=15,AZT+PPVOn=19。**AZT+PPVO治疗组与PBS(+载体)组相比病毒载量显著降低(p<0.01)。数据来源于两个分别的实验,只在一个实验中使用载体。
图3:PPVO与ART联用导致SIV感染的猕猴存活期更长。示出了在实验过程中存活的动物的数量。与其他所有组相比,PPVO+ART导致死亡率下降,生存期延长。所有死亡的动物均死于免疫缺陷相关综合征。
图4:ART导致SIV病毒载量减少,而PPVO不导致SIV病毒载量减少。示出了细胞相关的病毒载量,它与SIV血浆病毒载量相关。给出了每组的平均值(n=2-4)。在ART以及ART+PPVO组中可能观察到快速的病毒反弹。
图5A:PPVO治疗导致SIV感染的猴中CD4+细胞恢复。给出了各组在指定时间点相对于基线的CD3+CD4+细胞/μl血液的绝对百分数的平均值(n=2-4只动物)。PPVO导致CD3+CD4+细胞数稳定或者甚至增加,而单独ART组的动物则发生CD3+CD4+细胞损失。
图5B:PPVO治疗导致SIV感染的猴中CD4+细胞恢复。给出了各组在指定时间点的CD3+CD4+细胞/μl血液的绝对数以及平均值。带有颜色的方框中的数字分别表示所有组在感染前的CD3+CD4+细胞/μl血液的平均绝对数或各组在感染后59周的CD3+CD4+细胞/μl血液的平均绝对数;□治疗期;*ART:感染后53周;**PPVO:失去一只动物的数值。PPVO治疗导致CD3+CD4+细胞数稳定或者甚至增加,而单独ART组的动物则发生CD3+CD4+细胞损失(直到治疗后不久,例如第63周)。
图6:PPVO治疗导致CD3+CD8+细胞数高于基线。给出了在指定时间点相对于基线的CD3+CD8+细胞/μl血液的绝对百分数(n=2-4只动物)。PPVO+ART导致超过基线值,并且在增加CD3+CD8+细胞方面比单独的PPVO更有效。
本发明涉及:
1.副痘病毒与至少一种另外的抗病毒剂组合在制备治疗病毒性疾病的药物中的应用。
本发明还涉及副痘病毒在生产与至少一种另外的抗病毒剂联合治疗病毒性疾病的药物中的应用。本发明另一方案涉及副痘病毒在治疗病毒性疾病患者中的应用,其中向所述患者施用至少一种另外的抗病毒剂以治疗所述的病毒性疾病。另外,本发明还涉及病毒性疾病的治疗方法,其中副痘病毒与其他抗病毒剂联合施用。
根据本发明,副痘病毒应当理解为副痘病毒科的病毒,例如羊副痘病毒(Parapoxvirus ovis)、羊副痘病毒D1701株、羊副痘病毒NZ-2株、羊副痘病毒NZ-7株、羊副痘病毒NZ-10株或口疮病毒(例如orf-11)。
本发明还涉及通过使用适当的细胞系统传代或适应而获得的上述副痘病毒株的衍生物与在ART和/或HAART中有效的物质组合在生产对抗人类和动物病毒感染的药物中的应用,所述细胞系统例如是人细胞,如WI-38、MRC-5,猴细胞,例如Vero细胞,牛细胞,例如BK-K13A47/Reg或MDBK,和牛细胞,如MDOK。
另外,本发明还涉及上述毒株及其传代和适应变体的部分或片段与在ART和/或HAART中有效的物质组合的应用。根据本发明,病毒的部分或片段应当理解为整个病毒或其基因组核酸的基因组或亚基因组片段,或病毒的其他成分,它们通过合适的载体如痘苗病毒在合适的系统如成纤维细胞培养物中表达。在一个优选变化方案中,本发明的副痘病毒的部分或片段通过常规方法例如过滤或层析来纯化。在另一个优选变化方案中,本发明的副痘病毒的部分或片段通过本领域技术人员公知的方法重组产生。根据本发明,病毒性疾病是病毒感染引起的或与病毒感染有关的所有人类和动物疾病。
在本发明的一个优选变化方案中,所述抗病毒剂是抗逆转录病毒剂。
2.本发明还涉及根据第1项的应用,其中所述病毒性疾病是HIV感染和/或AIDS。
3.本发明还涉及根据第1或2项的应用,其中所述副痘病毒是羊副痘病毒、羊副痘病毒D1701株、羊副痘病毒NZ2株、羊副痘病毒、羊副痘病毒NZ-7株、羊副痘病毒NZ-10株或羊副痘病毒orf-11株。在本发明的另一个变化方案中,所述副痘病毒是通过将这些毒株传代而获得的副痘病毒。
4.本发明还涉及根据第1至3项之一的应用,其中所述副痘病毒以灭活形式存在。副痘病毒的灭活通过本领域技术人员公知的病毒灭活方法进行。在一个优选变化方案中,副痘病毒用欧洲专利EP-B1-0312839所述的方法灭活。
5.本发明还涉及根据第1至4项之一的应用,其中所述病毒性疾病的治疗导致患者的病毒载量降低。根据本发明,病毒载量的降低被理解为特别是患者体内病毒颗粒数量的减少。
6.本发明还涉及根据第1至5项之一的应用,其中所述病毒性疾病的治疗引起免疫系统的重建。根据本发明,免疫系统重建的特征在于血液中CD3+和CD4+细胞的浓度升高。在本发明的一个优选方案中,免疫系统重建的特征在于血液中CD4+和CD8+细胞的浓度升高。在本发明的另一个优选方案中,免疫系统重建的特征在于血液中CD4+和CD8+和CD3+细胞的浓度升高。在本发明的另一个优选方案中,免疫系统永久性地,即持久地重建。
7.本发明还涉及根据以上第1至6项之一的应用,其中所述病毒性疾病的治疗导致患者血液中CD4+和/或CD8+细胞增多。血液中CD4+和CD8+细胞的浓度同时升高是特别优选的。
8.本发明还涉及根据以上第1至7项之一的应用,其中所述抗病毒剂是用于HAART治疗的药物。本发明还涉及根据以上第1至7项之一的应用,其中所述抗病毒剂是用于ART治疗的药物。
9.本发明还涉及根据以上第1至8项之一的应用,其中所述抗病毒剂包含来自Gilead Sciences的Viread(延胡索酸替诺福韦(tenofovir disproxil fumarate),TDF)、来自Gilead Sciences的EmtrivaTM(恩曲他滨,FTC)、来自Bristol-Myers Squibb的Videx和VidexEC(去羟肌苷,ddI)、来自Bristol-Myers Squibb的Zerit和ZeritXR(司他夫定,d4T)、来自GlaxoSmithKline的Epivir(拉米夫定,3TC)、来自GlaxoSmithKline的Retrovir(齐多夫定,AZT)、来自GlaxoSmithXline的Ziagen(阿巴卡韦,ABC)、来自GlaxoSmithKline的Combivir(AZT和3TC)、来自GlaxoSmithKline的Trizivir(AZT、3TC和ABC)、来自Roche Laboratories的Hivid(扎西他滨,ddC)、来自Bristol-MyersSquibb的Sustiva(依法韦仑,EFV)、来自Boehringer Ingelheim的Viramune(奈韦拉平,NVP)、来自Agouron Pharmaceuticals的Rescriptor(地拉韦啶,DLV)、来自Bristol-Myers Squibb的ReyatazTM(atazanavir,ATV)、来自Abbott Laboratories的Norvir(利托那韦,RTV)、来自GlaxoSmithKline的Agenerase(安泼那韦,APV)、来自Abbott Laboratories的Kaletra(洛匹那韦/利托那韦,LPV/RTV)、来自Agouron Pharmaceuticals的Viracept(那非那韦,NFV)、来自Merck&Co.的Crixivan(茚地那韦,IDV)、来自Roche Laboratories的Fortovase(沙奎那韦,SQV-SGC)、来自Roche Laboratories的Invirase(沙奎那韦,SQV-HGC)、来自Roche Laboratories的FuzeonTM(恩夫韦地,T-20)、来自Immune Response Corp.的Remune、来自JanssenResearch Foundation Worldwide的Etravirine(TMC-125,R-165335)、来自Shionogi&Co.Ltd.的卡普韦林、来自Pfizer的UK-427857或来自Gilead Sciences的替诺福韦(PMPA)或另外一种抗病毒或免疫调节药物作为活性成分。
特别优选地,本发明还涉及根据以上第1至8项之一的应用,其中所述抗病毒剂包含AZT或3TC或PMPA作为活性成分。
10.本发明还涉及根据以上第1至9项之一的应用,其中所述疾病的治疗引起树突细胞或其他抗原呈递细胞的成熟和/或刺激。
本发明的药物组合物可以以口服形式给药,例如但不限于正常的和肠溶衣片剂、胶囊、丸剂、粉剂、颗粒剂、酏剂、酊剂、溶液、悬液、糖浆、固体和液体气雾剂和乳剂。也可以以非肠胃形式给药,例如但不限于药学领域技术人员公知的静脉内、腹膜内、皮下、肌肉内等形式。本发明的药物组合物可以通过局部应用适宜的鼻内载体以鼻内形式给药,或者使用本领域技术人员公知的透皮递送系统通过透皮途径给药。
本发明的药物组合物的剂量方案由本领域技术人员考虑多种因素来选择,这些因素包括但不限于接受者的年龄、体重、性别和医学状况、所治疗疾病的严重程度、给药途径、接受者的代谢水平和排泄功能、使用的剂型。
本发明的药物组合物优选地在给药前配制,并且包含一种或多种药学可接受的赋形剂。赋形剂是惰性物质,例如但不限于载体、稀释剂、调味剂、增甜剂、润滑剂、增溶剂、悬浮剂、粘合剂、药片崩解剂和包囊材料。
在另一个实施方案中,本发明的药物制剂包含与该制剂的其他成分相匹配并且对接受者无害的一种或多种药学可接受的赋形剂。在制备本发明的组合物时,活性成分可以与稀释剂混合,或者包封于载体内,该载体可以是胶囊、包囊、纸或其他容器的形式。载体可以用作稀释剂,可以是作为媒介物的固体、半固体或液体材料,或者可以是含有例如可达10重量%活性药物组合物的片剂、丸剂、粉剂、锭剂、酏剂、悬浮剂、乳剂、溶液、糖浆、气雾剂、软膏剂,软和硬明胶胶囊、栓剂、无菌注射溶液和无菌包装的粉末剂的形式。
对于口服,活性成分可以与以下成分组合:口服的、无毒的药学可接受的载体,例如但不限于乳糖、淀粉、蔗糖、葡萄糖、碳酸钠、甘露醇、山梨糖醇、碳酸钙、磷酸钙、硫酸钙、甲基纤维素等;以及,任选地,崩解剂,例如但不限于玉米、淀粉、甲基纤维素、琼脂、膨润土、黄原胶、海藻酸等;任选地,粘合剂,例如但不限于明胶、聚明胶肽、天然琼脂、β-乳糖、玉米甜味剂、天然及合成树胶、阿拉伯胶、西黄蓍胶、藻酸钠、羧甲基纤维素、聚乙二醇、蜡等;和任选地,润滑剂,例如但不限于硬脂酸镁、硬脂酸钠、硬脂酸、油酸钠、苯甲酸钠、乙酸钠、氯化钠、滑石等。
对于粉末形式,载体可以是与磨碎的活性成分混合的磨碎的固体。活性成分可以与具有结合特性的载体以适当比例混合,并且压制成形成片剂所需的形状和大小。粉末和片剂优选地含有约1-约99重量%的活性成分,即本发明的新组合物。合适的固体载体是羧甲基纤维素镁、低熔点蜡和可可脂。无菌液体制剂包括悬浮剂、乳剂、糖浆和酏剂。活性成分可以溶解或悬浮于药学可接受的载体中,如无菌水、无菌有机溶剂或无菌水和无菌有机溶剂的混合液。
活性成分也可以溶解于合适的有机溶剂,例如含水丙二醇中。可以通过将磨碎的活性成分分散到水淀粉或羧甲基纤维素钠溶液或合适的油中来制备其他的组合物。
制剂可以是单位剂量形式,它是含有单位剂量的物理上不连续的单元,适合对人或其他哺乳动物给药。单位剂量形式可以是一个胶囊或片剂,或许多胶囊或片剂。“单位剂量”是经计算与一种或多种赋形剂结合产生所需疗效的本发明活性药物组合物的预定量。剂量可以从每次给药约103到约1012物理数量的病毒颗粒不等,或者基于每kg每天的颗粒物理数量。
本发明的药物组合物可以单次以日剂量给药,或者总的日剂量可以以分开的剂量每天2、3或更多次给药。当通过透皮形式给药时,当然优选连续给药。
本发明的其他方案通过以下的实施例进行说明。
实施例1:PPVO在体外诱导树突细胞成熟
树突细胞是在启动初次免疫应答中起主要作用的抗原呈递细胞。它们的表型和功能特征与它们的成熟阶段密切相关[11]。用PPVO刺激全血细胞导致DC成熟,从而将其转化为功能性状态,它们在这种状态下能够非常有效地诱导免疫应答:PPVO能够刺激CD14高单核细胞(图1)以及未成熟DC中的TNF-α表达。来自全血样品的CD14高单核细胞TNF-α的产生不限于健康供体,PPVO也刺激来自免疫抑制HIV患者以及移植患者的CD14高单核细胞中的TNF-α表达(图1)。另外,如来自健康和无免疫应答供体的血液中早期活化标记CD69的表达所见(数据未显示),PPVO刺激全血24小时导致T细胞(CD4+和CD8+)活化。因此,在免疫抑制患者,特别是HIV感染患者中,免疫应答的早期阶段看来可被PPVO影响。
实施例2:hu-PBL-SCID中的HIV
为了检测PPVO对HIV的活性,在hu-PBL-SCID模型中研究了这种免疫调节剂。简言之,向SCID小鼠中移植人PBMC。选择重建得到证实的动物,通过腹膜内注射进行HIVBal感染。在感染30分钟后开始治疗。每天两次口服AZT(100mg/kg/天),而PPVO通过腹膜内途径仅每周给药两次。经ELISA测定,一份PPVO剂量含有2×104抗原单位。安慰剂(不含热原的PBS和载体对照)按照相应的治疗程序使用。在HIV感染后第3周杀死小鼠。根据从脾组织中提取的RNA监测病毒载量。与安慰剂(PBS+载体)相比,PPVO治疗证明降低了HIV病毒载量。向标准抗逆转录病毒治疗(AZT)中加入PPVO导致HIV复制被更好地抑制—病毒载量显著降低(p<0.01,Kruskal-Wallis检验)约90%(图2)。
实施例3:SIV
hu-PBL-SCID小鼠代表HIV感染的急性期。HIV感染者的治疗通常在感染过程的后期开始。为了检查PPVO在临床上更相关的情况中的效力,使用SIV(猿免疫缺陷病毒,HIV的猿同源物)感染模型。
使14只恒河猴感染SIV。第一个治疗期开始于感染后(p.i.)8周慢性期开始时病毒血症之后,持续9周。4只动物用抗逆转录病毒疗法(ART)治疗,4只用PPVO治疗,4只用ART和PPVO治疗。2只动物用安慰剂处理作为对照。ART治疗每天皮下给药,而PPVO治疗通过肌肉注射仅每周给药两次。第2个和第3个为期8周的治疗期分别开始于感染后第22周和第51周,静脉内给予PPVO。
在整个实验过程中没有观察到PPVO的毒性。与ART或PPVO单独治疗组相比,PPVO+ART治疗组的存活动物的数量增加,生存期延长(图3)。这不是由于ART,因为在两个ART治疗组都观察到病毒载量降低,而仅在PPVO+ART组观察到生存期延长(图4)。如图5A和5B所示,在ART+PPVO组以及PPVO单独治疗组中,PPVO治疗导致CD4+细胞计数恢复(感染后第59周的平均数分别为452或390个CD3+CD4+细胞/μl血液),而ART单独治疗导致CD4+细胞持续损失(感染后第59周的平均数为33个CD3+CD4+细胞/μl血液)(图5A和5B)。
PPVO导致CD8+细胞增多,当与ART联用时甚至更有效(图6)。单独的ART不导致较高的CD8+细胞计数。CD4+/CD8+比例在几乎所有动物中均缓慢下降(数据未显示)。
即使在该难以治疗的SIV病模型中病毒载量未被降低,这些仍然是非常有意义的结果。由CD4+和CD8+细胞的增多可以看出,PPVO增强了这些慢性感染动物的T细胞应答。由ART+PPVO治疗组的生存期延长和存活动物数增高推断,对抗病原体的免疫防御增强。
参者文献
1.Weber,O.等人,Inactivated Parapoxvirus ovis(Orf virus)hasantiviral activity against hepatitis B virus and herpes simplex virus(灭活的羊副痘病毒(口疮病毒)对乙型肝炎病毒和单纯疱疹病毒具有抗病毒活性).J Gen Virol.,2003.84:p.1843-52。
2.Mayr,A.,Development of a non-immunising,paraspecificvaccine from attenuated pox viruses:a new type of vaccine(来源于减毒痘病毒的非免疫类特异性疫苗的研发:一种新型疫苗).New Microbiol,2003.26(1):p.7-12。
3.Powderly,W.,A.Landay和M.Lederman,Recovery of theImmune System With Antiretroviral Therapy-The End of Opportunism?(应用抗逆转录病毒治疗恢复免疫系统)JAMA,1998.280:p.72-7。
4.Parienti,J.,Cytokine therapy or structured treatment interruptionsin HIV infection:which is best?(HIV感染的细胞因子治疗或结构化治疗干预:哪一个最好?)Expert Opin.Pharmacother,2002.3(6):p.719-26。
5.Garcia,F.等人,The virological and immunological consequencesof structured treatment interruptions in chronic HIV-1 infection(慢性HIV-1感染中结构化治疗干预的病毒学和免疫学后果).AIDS,2001.15(9):p.F29-40。
6.Emery,S.等人,Pooled analysis of 3 randomized,controlled trialsof interleukin-2 therapy in adult human immunodeficiency virus type 1disease (成人1型免疫缺陷病毒病中3个随机控制白介素-2治疗试验的合并分析).J Infect Dis,2000.182(2):p.428-34。
7.Silvestri,G.和M.Feinberg,Immune intervention in AIDS(AIDS的免疫干预).(in:Immunology of Infectious diseases(传染病免疫学);eds:Kaufmann,S.H.E.;Sher A.;Ahmend,R,ASM Press,Washington,D.C.),2002.Chapter 30:p.453-77。
8.Letvin,N.L.和B.Walker,Immunopathogenesis andimmunotherapy in AIDS virus infections(AIDS病毒感染的免疫发病机理和免疫治疗).Nat Med,2003.9(7):p.861-6。
9.Mori,K.等人,Suppression of acute viremia by short-termpostexposure prophylaxis of simian/human immunodeficiency virusSHIV-RT-infected monkeys with a novel reverse transcriptase inhibitor(GW420867) allows for development of potent antiviral immuneresponses resulting in effcient containment of infection(通过用新型逆转录酶抑制剂(GW420867)短期暴露后预防猿/人免疫缺陷病毒SHIV-RT-感染的猴来抑制急性病毒血症可以发展强有力的抗病毒免疫应答,导致有效的感染抑制).J Virol,2000.74(13):p.5747-53。
10.Lu,W.等人,Therapeutic dendritic-cell vaccine for simian AIDS(用于猿AIDS的治疗性树突细胞疫苗).Nat Med,2003.9(1):p.27-32。
11.Richards,J.等人,Integrated genomic and proteomic analysis ofsignaling pathways in den dritic cell differentiation and maturation(树突细胞分化和成熟中信号传导途径的综合基因组和蛋白质组分析).AnnNY Mad Sci,2002.975:p.91-100。
Claims (12)
1.副痘病毒与至少一种另外的抗病毒剂组合在制备治疗病毒性疾病的药物中的应用。
2.副痘病毒在制备与至少一种另外的抗病毒剂联合治疗病毒性疾病的药物中的应用。
3.副痘病毒在治疗病毒性疾病患者中的应用,其中对所述患者施用至少一种另外的抗病毒剂以治疗所述病毒性疾病。
4.根据权利要求1-3中任一项的应用,其中所述病毒性疾病是HIV感染和/或AIDS。
5.根据权利要求1-4中任一项的应用,其中所述副痘病毒是羊副痘病毒、羊副痘病毒D1701株、羊副痘病毒NZ2株、羊副痘病毒NZ-7株、羊副痘病毒NZ-10株、羊副痘病毒orf-11株、或通过将所述任一种副痘病毒株传代而获得的副痘病毒。
6.根据权利要求1-5中任一项的应用,其中所述副痘病毒以灭活形式存在。
7.根据权利要求1-6中任一项的应用,其中所述病毒性疾病的治疗导致患者的病毒载量降低。
8.根据权利要求1-7中任一项的应用,其中所述病毒性疾病的治疗引起免疫系统的重建。
9.根据权利要求1-8中任一项的应用,其中所述病毒性疾病的治疗导致患者CD4+和/或CD8+细胞增多。
10.根据权利要求1-9中任一项的应用,其中所述抗病毒剂是用于HAART治疗的药剂。
11.根据权利要求1-10中任一项的应用,其中所述抗病毒剂包含AZT或3TC或PMPA作为活性成分。
12.根据权利要求1-11中任一项的应用,其中所述疾病的治疗引起树突细胞或其他抗原呈递细胞的成熟和/或刺激。
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EP2849774A4 (en) * | 2012-05-18 | 2015-11-25 | Otago Innovation Ltd | COMBINATION TREATMENTS AND COMPOSITIONS FOR WOUND HEALING |
EP3762020A1 (en) | 2018-03-07 | 2021-01-13 | Transgene | Parapoxvirus vectors |
HRP20221110T1 (hr) * | 2020-05-08 | 2022-11-25 | Aicuris Gmbh & Co. Kg | Parapoxvirus za kondicioniranje i liječenje infekcija uzrokovanih koronavirusom |
WO2023083950A1 (en) * | 2021-11-10 | 2023-05-19 | Aicuris Gmbh & Co. Kg | Parapoxvirus for preparing for and treatment of respiratory virus infections in combination with immunomodulators |
WO2023083943A1 (en) * | 2021-11-10 | 2023-05-19 | Aicuris Gmbh & Co. Kg | Parapoxvirus for preparing for and treatment of respiratory virus infections in combination with antivirals |
WO2024062098A1 (en) | 2022-09-23 | 2024-03-28 | Transgene | Recombinant pseudocowpox virus encoding an interleukin-12 |
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BRPI0513321A (pt) | 2008-05-06 |
DE602005016552D1 (de) | 2009-10-22 |
CA2573204C (en) | 2011-09-20 |
JP4897677B2 (ja) | 2012-03-14 |
BRPI0513321B1 (pt) | 2022-03-08 |
DK1765370T3 (da) | 2009-11-02 |
ATE442155T1 (de) | 2009-09-15 |
PL1765370T3 (pl) | 2010-02-26 |
US20100255032A1 (en) | 2010-10-07 |
CN103800382A (zh) | 2014-05-21 |
PT1765370E (pt) | 2009-09-23 |
US8343478B2 (en) | 2013-01-01 |
WO2006005529A1 (en) | 2006-01-19 |
CA2573204A1 (en) | 2006-01-19 |
JP2008505952A (ja) | 2008-02-28 |
EP1765370A1 (en) | 2007-03-28 |
ES2330540T3 (es) | 2009-12-11 |
HK1097467A1 (en) | 2007-06-29 |
EP1765370B1 (en) | 2009-09-09 |
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