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CN1086589C - 疫苗 - Google Patents

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CN1086589C
CN1086589C CN94194554A CN94194554A CN1086589C CN 1086589 C CN1086589 C CN 1086589C CN 94194554 A CN94194554 A CN 94194554A CN 94194554 A CN94194554 A CN 94194554A CN 1086589 C CN1086589 C CN 1086589C
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帕特里夏·M·莫米恩
内森里·M-J·加肯
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Abstract

本发明提供了疫苗组合物，含有一种水包油乳液，该乳液可任选地与3-脱氧酰基化单磷酰脂A和QS21相组合。该疫苗组合物是许多免疫应答的强有力的诱导剂。

Description

疫苗
本发明涉及新的疫苗制剂，及其生产方法以及该疫苗制剂在医学上的应用。特别是，本发明涉及一种水包油乳液。这种乳液包括生育酚、角鲨烯、吐温80、Span 85(司盘85)以及卵磷脂，并且具有有效的佐剂特性。含有一种来源于Quillaja Saponaria Molina的树皮的HPLC纯化的非毒性组分，QS21，和/或3脱氧酰基化的单磷酰脂A(3De-O-acylated monophosphoryl lipid A，3D-MPL)，以及这样的水包油乳液进行组合的疫苗也是本发明的一部分。
从GB 2220211(Ribi)知道了3脱氧酰基化的单磷酰脂A。从化学上说，它是一种具有4，5或6酰基化的链的3脱氧酰基化的单磷酰脂A的混合物，由Ribi Immunochem Montana制备。在国际专利申请NO.92/116556中公开了3脱氧酰基化的单磷酰脂A的一种优选形式。
QS21是一种来自南美的Quillaja Saponana Molina树的树皮的经Hplc纯化的皂角苷(Saponin)的非毒性组分，其生产方法公开(以QA 21形式)于美国专利NO.5,057,540中。
水包油乳液本身是现有技术中已知的，并且已有人建议可将其用作为佐剂组合物(EPO 399843)。
本发明是基于下列惊人发现，与现有技术的乳液不相同的本发明的水包油乳液，含有生育酚或者含有结合了QS21和/或3D-MPL的生育酚，从而增强了对给定抗原的免疫应答。这种增强作用比迄今为止以前的所有同类制剂能提供更好的免疫应答。
另外，当将本发明的水包油乳液与3D-MPL和QS21一起配制时是IgG2a产生和TH1细胞应答的优选的刺激剂。这是有利的，因为在细胞介导的应答中已知包含有TH1应答。的确在鼠中IgG2a的诱导是与这样一种免疫应答相关的。
例如以这种方式组合的HIV抗原gp120的疫苗制剂可强有力地增效诱导对gp 120蛋白质的特异的免疫应答。
观察到可能诱导强的细胞溶解的T淋巴细胞应答的结果很有意义，因为在一些动物模型中已经证明这种细胞应答诱导了抵抗疾病的保护作用。
本发明人已经证明，佐剂QS21和3D-MPL以及在一起的水包油乳液与一种抗原结合后在脾脏中导致对CS蛋白质特异性的CTL的强力诱导作用。QS21本身也增强了CTL的诱导，而3D-MPL不能。
当胞内合成靶抗原时(例如由病毒，胞内细菌产生的感染，或在肿瘤中)容易看到CTL的诱导作用，因为由抗原的蛋白质裂解产生的肽可以进入合适的加工途径，导致以与I类分子相结合形式呈现在细胞膜上。但是，一般来说，预形成的可溶性抗原没有到达该加工和呈现途径，并且没有诱导I类范围内的CTL。因此，可诱导抗体和T辅助应答的常规的非活性疫苗一般不能诱导CTL介导的免疫应答。两种佐剂QS21和3D-MPL与水包油乳液结合在一起能够克服基于重组蛋白质的疫苗的严重的局限性，并可诱导更宽范围的免疫应答。
已经证明在鼠模型系统中特异于CS蛋白质的CTL可抵抗疟疾(Romero等人，Nature 341：323(1989))。在人试验中，当将志愿者用恶性疟原虫的被辐射过的子孢子体进行免疫接种后，可显示出抵抗随后的疟疾的进攻，显示出诱导出了特异于CS表面抗原决定簇的CTL(Malik et al.Proc.Natl.Acad.Sci.USA 88：3300(1991))。
可诱导出对以重组分子形式给药的一种抗原具特异性的CTL的能力是与疟疾疫苗的研制相关的，因为基于免疫应答的产生及其特性，使用经辐射的子孢子体是不切实际的。
RTS是一种杂合蛋白质，它基本上含有借助于乙肝表面抗原的pre S2部分的四个氨基酸连接到乙肝病毒的表面(S)抗原上的恶性疟原虫的环子孢子体(CS)蛋白质的整个C末端部分。其完整结构公开于共同待批国际专利申请NO.PCT/EP 92/02591，该申请要求了UK专利申请NO.9124390.7的优先权，其公开号为WO 93/10152。当在酵母中表达时产生出脂蛋白颗粒形式的RTS，并且当以与HBV的S抗原共表达时产生出已知为RTS，S的混合颗粒。
除了人免疫缺陷病毒和疟疾疫苗外，诱导CTL应答的能力有利于抗单纯性疱疹病毒，巨细胞病毒以及通常的具有胞内生活期的病原体的所有病例的疫苗。
同样，将重组肿瘤抗原和两种佐剂组合后可诱导特异于已知肿肿瘤抗原的CTL。这为研制抗癌疫苗提供了条件。
在一些系统中，将3D-MPL和QS21以及水包油乳液结合起来能够协同地增强干扰素γ的产生。本发明人利用已知的名为gD2t的单纯性疱疹抗原证明了3D-MPL和QS21与水包油乳液组合在一起的潜力。gD2t是一种从HSV-2上切下的可溶性糖蛋白D，并且是采用Berman等人的方法(Science 222 524-527)在CHO细胞中产生的。
IFN-γ的分泌是与抗胞内病原体，包括寄生虫，细菌和病原体的保护性应答相关的。由IFN-γ对巨噬细胞的激活增强了胞内对微生物的杀伤力以及增强Fc受体的表达。也可能存在直接的细胞毒性，尤其是在与淋巴毒素(TH1细胞的另一种产物)进行增效作用时。IFN-γ既是NK细胞的诱导剂又是其产物，NK细胞是保护作用的主要的固有的效应子。通过IFN-γ或者其他机制进行的TH1型应答为IgG2a免疫球蛋白同型提供了优先帮助。
糖蛋白D定位于病毒包膜上，并且也存在于受感染细胞的胞质中(Eisenberg R.J.等人J.of Virol.1980 35：428-435)。它含有包括信号肽在内的393个氨基酸并且具有约60KD的分子量。在所有的HSV包膜糖蛋白中，它可能是得到最详细表征的一种(Cohen等人，J.Virology 60：157-166)。已知在体内它对于病毒粘附到细胞膜上起着关键的作用。而且，已证明糖蛋白能够在体内诱导出中和抗体(Eing等人，J.Med.Virology 127：59-65)。但是，尽管在患者血清中存在高效价的中和抗体，潜伏的HSV2病毒仍能被重新激活并诱导疾病复发。因此，显然仅具有诱导中和抗体的能力不足于控制疾病。
为了防止疾病复发，任何疫苗需要不仅刺激中和抗体，而且激发由T细胞，特别是毒性T细胞介导的细胞免疫作用。
对于gD2t例子，它是308个氨基酸的HSV2糖蛋白D，它含有天然存在的糖蛋白的第1-306个氨基酸，在该被截短的蛋白质的C-末端添加了天冬酰胺和容氨酰胺。这种蛋白质形式包括信号肽，将该信号肽裂解后产生成熟的283氨基酸蛋白质。在Genentech的欧洲专利EP-B-139 417中已描述了在中国仓鼠卵细胞中生产这样一种蛋白质。
该成熟的被截短的糖蛋白D(rgD2t)或从哺乳动物细胞中分泌的等同蛋白质优先用于本发明的疫苗制剂中。
在患有生殖器疱疹的豚鼠模型中本发明的制剂可十分有效地诱导保护性免疫作用。甚至在具有非常低剂量抗原(例如低至5μgrgD2t)时该制剂可保护豚鼠抵抗初次感染，并且也激发了特异性的中和抗体应答。本发明人利用本发明的制剂也证实了在鼠中效应细胞介导的TH1型应答。
因此，在一个优选实施方案中，本发明提供了一种含有与3-脱氧酰基化的单磷酰脂A，QS21和一种水包油乳液相组合的抗原的疫苗或药物制剂，该水包油乳液含有一种可代谢的油，例如角鲨烯，α-生育酚和吐温80。这样一种制剂适合于很多的单价或多价疫苗。另外，该水包油乳液可含有span 85。3-脱氧酰基化的单磷酰脂A的一种优选形式公开于公开号为NO.92116556的Smithkline BeechamBiologicals s.a.的国际专利申请中。
该水包油乳液可以单独使用或与其他佐剂或免疫刺激剂结合起来使用，因此本发明的一个重要实施方案是一种含有角鲨烯或另一种可代谢油，α-生育酚和吐温80的水包油制剂。该水包油乳液还可含有span 85和/或卵磷脂。
优选的疫苗制剂含有能够引发抗人或动物病原体的免疫应答的抗原或抗原组合物，所述抗原或抗原组合物来源于HIV-1(例如gp120或gp160)，任何猫的免疫缺陷病毒，人或动物疱疹病毒，例如gD或其衍生物或立即早期蛋白如来源于HSV1或HSV2的ICP27，巨细胞病毒((尤其是人)(例如gB或其衍生物)，水痘带状疱疹病毒(例如gpI，II或III)，或者来源于例如已肝病毒的肝炎病毒，例如乙肝表面抗原或其衍生物，甲肝病毒，丙肝病毒和戊型肝炎病毒，或者来自于其他病毒病原体，例如呼吸道合胞体病毒，人乳头瘤病毒或流感病毒、或者来源于细菌病原体如沙门氏菌、奈瑟氏菌、螺旋体(例如OspA或OspB或其衍生物)，或者衣原体，或博德特氏菌例如P.69，PT和FHA，或来源于寄生虫如疟原虫或者弓形体。
该制剂还可含有一种抗肿瘤抗原并适用于采用免疫治疗法治疗癌症。
在一种适于免疫治疗的患有B细胞淋巴瘤的动物模型中，当在第0天时将BCL-1鼠淋巴瘤细胞静脉注射到Balb/c小鼠中，并在第3天，10天和20天用BCL-1同种异型给小鼠免疫接种，就抗体效价和存活率(该组为存活率为100％的唯一组)而言，SB62/MPL/QS21制剂被证明为最有效力。同样，该制激发针对所包含的抗原的细胞毒性T淋巴细胞的能力，使其成为作为癌抗原制剂的良好的候选物(例如用于通过活性免疫接种而对肿瘤进行免疫治疗的黑色素瘤抗原MAGE-1和MAGE-3)。
该制剂还适用于与疱疹的轻颗粒一起使用，例如描述于国际专利申请NO.PCT/GB 92/00824，以及国际专利申请NO.PCT/GB 92/00179的制剂。
乙肝表面抗原的衍生物是本领域内熟知的，并且特别包括那些在欧洲专利申请EP-A-414374；EP-A-0304578，和EP 198-474中描述的PreS1，PreS2 S抗原。在一个优选的方面，本发明的疫苗制剂包括HIV-1抗原，gp120，尤其是当在CHO细胞中表达时，在另一实施方案中，本发明的疫苗制剂包括如上文中定义的gD2t。
在本发明的又一方面，提供了如本发描述的在医学上使用的疫苗。
QS21与3D-MPL的比例通常是在1∶10至10∶1的范围，优选的是1∶5-5∶1并且实质上经常是1∶1。达到最适增效作用的优选范围是2.5∶1到1∶1的3D MPL∶QS21。当给人使用时通常疫苗中存在的QS21与3D MPL的比例为1μg-100μg/每剂量的范围，优选的是10μg-50μg/每剂量。水包油乳液通常含有2-10％的角鲨烯，2-10％α-生育酚以及0.3-3％吐温80。优选的是角鲨烯与α-生育酚的比例是等于或者低于1，因为这样使乳液更稳定。还可以存在1％含量的Span 85。在某些情况下，本发明的疫苗进一步含有一种稳定剂是有利的。
通常疫苗的制备可参见New Trends and Developments in Va-ccines，edited by Voller et al.，University Park Press，Baltimore，Maryland，U.S.A.1978。脂质体内进行包埋的方法例如可参见Fullerton，美国专利4,235,877的描述。蛋白质与大分子的结合例如公开于由Likhite的美国专利4,372,945以及Armor等人的美国专利4,474,757。
所选择单疫苗剂量中蛋白质的量为在典型的接种人中诱导产生免疫保护应答而无显著的毒副作用所需的量。该量将随所使用的特定免疫原以及如何提供而变化。通常，单个剂量含有1-1000μg的蛋白质，优选的是1-100μg，更优选的为4-40μg。采用包括观察个体中合适免疫应答的标准研究确定用于特定疫苗中的最适量。在首次免疫接种之后，受试个体可接受一次或者适当间隔的几次加强免疫接种。
本发明的药剂可用于预防和治疗目的。
因此，一方面，本发明提供了一种治疗方法，该方法包括给患者施用有效量的本发明的疫苗。
下面实施例阐明本发明。
                      实施例1
含有HIV-1的gp 120抗原的疫苗制剂
制备两种佐剂制剂，每种含有下列水包油乳剂成分。
SB 26：5％角鲨烯，5％生育酚，0.4％吐温80；颗粒大小是500nm。
SB 62：5％角鲨烯，5％生育酚，2.0％吐温80；颗粒大小是180nm。
1(a)乳剂SB 62的制备(2倍浓缩)
将吐温80溶于磷酸缓冲盐水(PBS)中得到溶于PBS中的2％的溶液。为了提供100ml两倍浓缩乳液，将5克DLα生育酚和5ml角鲨烯涡流以便彻底混合。加入90ml PBS/吐温溶液并彻底混合。然后将得到的乳液通过一个注射器并且最后利用MllOS微射流机器进行微射流。得到的油滴具有约180nm的大小。
1(b)乳液SB26的制备
以类似的方式利用0.4％吐温80制备该乳液。
1(c)以类似的方式制备表1中描述的其他乳液。下列实施例中详细描述了检测这些乳液的试验。
1(d)gp120 QS21/3D MPL水包油制剂的制备
向1a)或b)或c)乳液中加入某体积的两倍浓缩的rgp 120(20μg或100μg)并且混合。将它与50μg/ml的3D-MPL和20μg/ml的QS21合并，得到最后的制剂。按照盐含量和pH值调整缓冲液。
表3显示利用来自HIV的gp120和50μg/ml 3D-MPL(MPL)以及20μg/ml的QS21的SB26的效果。结果显示在第二次(PII)和第三次(PIII)接种后效价的几何平均值(GMT)，以及对淋巴细胞增殖和γ干扰素产生作出的细胞介导的应答(CMI)。
                     实施例2
引言：一种HIV gp120乳液系统的评估
在该实验中，对四个乳液[SB26，SB62，SB40，SB61]进行比较。对各个制剂成分(抗原，乳液，3D-MPL，QS21)的效应进行评估。
2(b)所使用的动物试验组
使用22组，每组5个动物，使每组接受不同的疫苗制剂。
-1-4组：gp120(10μg)/无乳液±[3D-MPL，QS21]
-5-9组：gp120(10μg)/SB26±[3D-MPL，QS21]
-10组：无抗原/SB26+[3D-MPL，QS21]
-11-12组：gp120(10μg)/SB62±[3D-MPL，QS21]
-13-16组：gp120(10μg)/SB40±[3D-MPL，QS21]
-17-20组：gp120(10μg)/SB61±[3D-MPL，QS21]
-21-22组：gp120(5μg)/SB26±[3D-MPL，QS21]
-分析：抗gp120W61D的抗体效价以及同型分析(所有组)
2(c)免疫接种以及抽血时间表
-用gp120W61D对动物进行免疫接种，所述gp120W61D是配制于每剂量存在5μg 3D-MPL和5μg QS21的不同的油水乳液中。阴性对照接受没有抗原的等同制剂。
-在0和14天时皮下注射免疫接种动物。所给药的每次注射剂量为100μl。
-在免疫接种前(0天)以及在免疫接种之后第14天(第一次接种后)，第21以及28(第二次接种后第7和第14天)天获取血样品。
2(d)血清学应答分析：
-第一次接种后和第二次接种后的14天的血清学应答是采用针对gp120W61D的直接ELISA检测法进行评估的。
-用免疫接种之后小鼠中诱导出的gp120W61D特异性抗体的同型也对第二次接种后14天的应答进行表征。
3.结果和讨论
结果描绘于表2中。
a)在存在或不存在3D-MPL/QS21的乳液的比较：
-将SB26，SB40或SB62乳液加入到抗原中诱导出更高的抗体效价。在没有免疫刺激剂情况下，gp120特异性抗体基本上是IgG1。
-加入免疫刺激剂3D-MPL和QS21诱导了巨大的血清学应答并且抗体从IgG1型转变为IgG2a/IgG2b：这与细胞介导的免疫相关。
优选的组合是[SB26+MPL+QS21]。
c)gp120/SB26制剂：
在8组和9组之间没有观察到血清学应答之间的显著差异：在本制剂其他成分之前或之后加入gp120。
d)抗原剂量：
配制于SB26中的5和10μg gp120诱导了高血清应答(5-8组以及21-22组)。
                         实施例3
HSV rgD2t制剂
按照实施例1(a)中提出的类似方式，制备含有单纯疱疹抗原rgD2t的制剂并用于免疫接种豚鼠。所述制剂诱导出抵抗豚鼠模型中复发和起始疾病的保护作用。
                        实施例4
利用个体基因型作为免疫原筛查用于诱导保护性抗淋巴瘤应答的佐剂。
利用来自BCL1淋巴瘤细胞的个体基因型给Balb/c小鼠进行治疗性免疫接种。
由Yefenoh等人对BALB/C B细胞淋巴瘤模型进行了综述。Curr-ent opinions Immunobiology 1993 5：740-744。
用104肿瘤细胞在0天时注射(ip)的10只小鼠的组，并用溶于不同佐剂制剂中的100μg的KLH偶合的抗BCL1抗原决定簇的免疫球蛋白(KLH/Ig：1/1的比例)在第3天，10天，20天免疫接种(在背部皮下注射)。对抗KLH和抗个体基因型的血清抗体水平以及鼠死亡率进行了监测。
所检测的制剂：
组号     佐剂                        MPL：10μg
1        无(无抗原)                  QS21：10μg
2        无
3        弗氏佐剂
4        明矾
5        明矾/MPL
6        明矾/MPL/QS21
7        QS21
8        MPL/QS21
9       SB62MPL
10      SB62/MPL/QS21
12-15组：没有抗原的不同佐剂
与其他组相比，制剂8、9、10的行为均较好。在抗体效价以及存活率两方面，制剂10表现为最有效力(生存率为100％的唯一组)。
                       实施例5
RTS，S的不同制剂
a)在猴中的评价
在国际专利申请No.WO 93/10152中描述了RTS，S并且制成制剂用于给Rheusus免疫接种。每组有5个动物：
I组      RTS，S，3D-MPL(50μ)，Al(OH)3
II组     RTS，S，QS21(20μ)，Al(OH)3
III组    RTS，S，3D-MPL(50μ)，QS21(20μ)
IV组     RTS，S，3D-MPL(50μ)，QS21 Al(OH)3
V组      RTS，S，3D-MPL(10μ)，QS21 Al(OH)3
VI组     RTS，S，3D-MPL(50μ)，QS21 SB60
给动物接种并且在第一次免疫接种之后14天以及第二次免疫接种之后12天取血，并检测其抗乙肝表面免疫球蛋白。如在图1中可看到的，接受SB60中的RTS，S的动物具有的抗体效价几乎比任何其他组高出6倍。
b)用小鼠对RTS，S的各种制剂进行评估
7组动物接受下列制剂
1组      RTS，S SB26
2组      RTS，S QS21 3D-MPL
3组      RTS，S QS21 3D-MPL SB62
4组      RTS，S 3D-MPL Al(OH)3
5组      RTS，S Al(OH)3
6组      空白
7组      阴性对照
(RTS，S-5μg/剂量，3D-MPL 5μg/剂量，QS21 5μg/剂量)
给动物接种并且在第一次接种后15天以及在第二次接种之后7天和15天取血，并检测抗HBSAg抗体亚型。如在图2中可看到的，用QS21和3D-MPL配制的乳液SB62优先地和以协同增效方式加强IgG2a抗体应答，而单独的SB62或3D-MPL/QS21诱导极少的IgG2a应答。
实施例6：对不同的B burgdorferi OspA制剂的评估
6.1不同的B burgdorferi ZS7 OspA脂蛋白制剂的评估
在欧洲专利申请0418 827(Max Plank et al)中描述了B bur-gdorferi的OspA脂蛋白。
在balb/c鼠中检测下列制剂
1. OspA+Al(OH)3
2. OspA+Al(OH)3+3D-MPL(10μ)
3. OspA+Al(OH)3+3D-MPL(30μ)
4. OspA+Al(OH)3+3D-MPL(10μ)+QS21(5μ)
5. OspA+Al(OH)3+3D-MPL(30μ)+QS21(15μ)
6. OspA+SB60+3D-MPL(10μ)+QS21(5μ)
7. OspA+SB60+3D-MPL(30μ)+QS21(15μ)并且在第一次接种之后7天以及在第二次接种之后7天(在0天和14天接种)研究抗体效价和亚型。
在图3和图4中以图形式描述结果，并且证明本发明的制剂诱导出高水平的抗体并且它们优先的是IgG2a亚型。
                       实施例7
a)HSV-2 ICP27
在0天和14天时在后脚爪用各种NS1-ICP27制剂给雌性Balb/c小鼠免疫接种。每次注射含有5μg的NS1-ICP27以及SB26水包油乳液，QS21(10μg)和MPL(25μg)的组合物。在28天时取出腘淋巴结细胞并在体外用转染了ICP27基因的同系P815细胞进行刺激。用转染了ICP27和P815 ICP27阴性对照的P815靶细胞检测该培养物的特定的细胞溶解活性。
对于不同的免疫接种组以不同的效应子∶靶(E∶T)比例的具体裂解结果如下所示：ICP 27(5μg)E∶T    P815  转染了ICP27克隆121的P815100∶1  -1    030∶1   -2    -310∶1   3     03∶1    1     01∶1    2     20.3∶1  2     2ICP 27(5μg)+MPL(25μg)E∶T    P815  转染了ICP27克隆121的P815100∶1  5      730∶1   2      210∶1   1      23∶1    -1     -11∶1    -2     -20.3∶1  -4     -1ICP 27(5μg)+QS21(10μg)E∶T     P815  转染了ICP27克隆121的P815100∶1   4     1730∶1    5     1010∶1    3     73∶1     4     51∶1     3     50.3∶1   0     1ICP 27(5μg)+SB26E∶T     P815  转染了ICP27克隆121的P815100∶1   5     2030∶1    1     1910∶1    2     123∶1     -2    71∶1     1     50.3∶1   1     2ICP 27(5μg)+MPL(25μg)+QS21(10μg)E∶T     P815  转染了ICP27克隆121的P815100∶1   4     1330∶1    5     1210∶1    4     173∶1     1     31∶1     0     30.3∶1   -1    -2ICP 27(5μg)+MPL(25μg)+QS21(10μg)+SB26E∶T     P815  转染了ICP27克隆121的P815100∶1   2     2030∶1    0     1710∶1    3     193∶1     3     81∶1     1     60.3∶1   2     3在免疫接种组中获得的低ICP27特异性裂解％ICP27(5μg)+QS21(10μg)ICP27(5μg)+SB26ICP27(5μg)+MPL(25μg)+QS21(10μg)ICP27(5μg)+MPL(25μg)+QS21(10μg)+SB26而ICP27(5μg)ICP27(5μg)+MPL(25μg)是阴性
因此这些数据显示由重组NS1-ICP27在单独的水包油乳液或与QS21和MPL一起；或与QS21一起诱导出CTL。
b)用不同疫苗(NS1-ICP27/NS1-ICP27 MPL+QS21/NS1-ICP27 SB26＝MPL和QS21/仅佐剂)在脚爪处给5个Balb/c小鼠为一组的各组免疫接种。一个剂量含有10μg NS1-ICP27，10μg MPL和10μg QS21。在0天和7天进行两次免疫接种。在14天用5.2×103TCID50的HSV2菌株MS攻击小鼠。一直到攻击后14天都记录是否出现带状疱疹样的损伤和死亡。
在大肠杆菌中表达出了与流感病毒NS1片段的融合蛋白形式的HSV2的ICP27。在鼠带状疱疹样模型中对该纯化重组蛋白与MPLQS21制剂的组合物的保护效率进行评估。在用与MPL+QS21或与水包油乳液(SB26)+MPL和QS21组合的NS1-ICP27进行两次免疫接种的Balb/c小鼠可完全抵抗疾病(无带状疱疹样损伤)以及在HSV2野生型攻击之后没有死亡发出。相反，在单独用NS1-ICP27或用NS1-ICP27与SB26但没有MPL和QS21进行相组合的疫苗对小鼠进行免疫接种后没有观察到保护作用。
                                           表1
                                     两倍浓缩的载体
乳液SB 生育酚％ 角鲨烯％ 吐温80％    Span 85％    卵磷脂％         大小
    2626.163646162     555555     555555     0.40.40.60.812      000000      00.10000      500nm 90-100％800nm 10-0％500nm500nm500nm250-300nm180nm
    4040.1606566     55555     55555     0.40.410.40.4      1111.52      00.1000      500nm 80-100％800nm 20-0％500nm300nm500nm500nm
                                                   表2
                                  HIV gp 120W61D/     鼠免疫原性(94243)/BALB/C(F.P.)
   组号          免疫原(剂量)/制剂     ELISA效价(第二次接种后7天)     ％IgG1     ％IgG2a   ％IgG2b
    123456789111213141516171819202122          gP120 10μggP120 10μg+3D-MPL 5μggP120 10μg+QS21 5μggP120 10μg+3D-MPL+QS21gP120 10μg/SB26gP120 10μg/SB26+3D-MPLgP120 10μg/SB26+QS21gP120 10μg/SB26+3D-MPL+QS21SB26+3D-MPL+QS21/gP120 10μggP120 10μg/SB62gP120 10μg/SB62+3D-MPL+QS21gP120 10μg/SB40gP120 10μg/SB40+3D-MPLgP120 10μg/SB40+QS21gP120 10μg/SB40+3D-MPL+QS21gP120 10μg/SB61gP120 10μg/SB61+3D-MPLgP120 10μg/SB61+QS21gP120 10μg/SB61+3D-MPL+QS21gP120 5μg/SB26gP120 5μg/SB26+3D-MPL+QS21     4944164215155274912205873885102017816918570410348217393632028521948953209217＜5077515407375967325089242736     1005489229431732322925490317814-3174299918       0154602421557608377441567-501357061     03281842713211909425718-191314121
由LINEST计算出的gp120W61D的ELISA效价：5个单体效价的几何平均值
                                                        表3
                                           基于3D-MPL的制剂；HIV工程猴研究
           读数     GMT ELisa W61 D        GMT Neut.MN 体内DTH 体外CMI
           制剂   P11   P111     P11   P111     LP   IL-2     γIFN
    gp120(100μg)/油/水+MPL+QS21gp120(20μg)/油/水+MPL+QS21豚鼠中“过去的”gp120(100μg)/油/水+MPL   6052352026   934105015020064     1∶5001∶500   ＞1∶32001∶2400     ++   没有检测没有检测       ++

Claims (10)

1、一种疫苗组合物，包含有一种抗原和/或抗原组合物，QS21，3脱氧酰基化单磷酰脂A(3D-MPL)和水包油乳液，其中该水包油乳液具有下列组分：一种可代谢油，例如角鲨烯，α-生育酚和吐温80。
2、按照权利要求1中所述疫苗，其中QS21∶3D-MPL的比例是从1∶10到10∶1。
3、按照权利要求1或2所述疫苗组合物，能够在哺乳动物中激发针对该抗原或抗原组合物的细胞溶解性T细胞应答。
4、按照权利要求1-3任一项所述的疫苗组合物，它能够刺激干扰素γ的产生。
5、按照权利要求1-4任一项所述疫苗组合物，其中QS21∶3D-MPL的比例是从1∶1到1∶2.5。
6、如本文所述的一种疫苗组合物，其中包括来源于人免疫缺陷病毒、猫免疫缺陷病毒、单纯性疱疹病毒1型、单纯性疱疹病毒2型、人巨细胞病毒、甲、乙、丙或戊型肝炎病毒、呼吸道合胞体病毒、人乳头瘤病毒、流感病毒、沙门氏菌、萘瑟氏菌、螺旋体、衣原体、博德持氏菌、疟原虫或弓形体中的任何抗原或抗原组合物。
7、根据权利要求1-5任一项所述的疫苗，其中该抗原是肿瘤抗原。
8、权利要求1-5任一项所述组合物的应用，用于制造病毒，细菌或寄生虫感染的预防治疗的疫苗。
9、权利要求1-5任一项所述组合物的应用，用于制造病毒，细菌或寄生虫感染或癌症的免疫治疗的疫苗。
10、一种制备权利要求1-5所述疫苗组合物的方法，包括将QS21，3D-MPL和如权利要求1中定义的水包油乳液与一种抗原或抗原组合物进行混合。
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Families Citing this family (589)

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Publication number Priority date Publication date Assignee Title
GB9326253D0 (en) 1993-12-23 1994-02-23 Smithkline Beecham Biolog Vaccines
US5690942A (en) * 1995-06-02 1997-11-25 American Home Products Corporation Adjuvants for viral vaccines
GB9513261D0 (en) * 1995-06-29 1995-09-06 Smithkline Beecham Biolog Vaccines
PT909323E (pt) 1996-01-04 2007-06-04 Novartis Vaccines & Diagnostic ''bacterioferritina de helicobacter pilori''
GB9616351D0 (en) * 1996-08-02 1996-09-11 Smithkline Beecham Biolog Vaccine composition
US20030185830A1 (en) * 1997-02-25 2003-10-02 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US7517952B1 (en) * 1997-02-25 2009-04-14 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
US20060024301A1 (en) * 1997-02-25 2006-02-02 Corixa Corporation Prostate-specific polypeptides and fusion polypeptides thereof
GB9706957D0 (en) 1997-04-05 1997-05-21 Smithkline Beecham Plc Formulation
GB9711990D0 (en) * 1997-06-11 1997-08-06 Smithkline Beecham Biolog Vaccine
GB9712347D0 (en) * 1997-06-14 1997-08-13 Smithkline Beecham Biolog Vaccine
ES2500490T3 (es) * 1997-08-29 2014-09-30 Antigenics Inc. Composiciones que comprenden el adyuvante QS-21 y polisorbato o ciclodextrina como excipiente
GB9718901D0 (en) 1997-09-05 1997-11-12 Smithkline Beecham Biolog Vaccine
EP1009382B1 (en) * 1997-09-05 2003-06-18 GlaxoSmithKline Biologicals S.A. Oil in water emulsions containing saponins
GB9724531D0 (en) 1997-11-19 1998-01-21 Smithkline Biolog Novel compounds
TWI239847B (en) 1997-12-02 2005-09-21 Elan Pharm Inc N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease
US6761888B1 (en) 2000-05-26 2004-07-13 Neuralab Limited Passive immunization treatment of Alzheimer's disease
US6923964B1 (en) 1997-12-02 2005-08-02 Neuralab Limited Active immunization of AScr for prion disorders
US6913745B1 (en) 1997-12-02 2005-07-05 Neuralab Limited Passive immunization of Alzheimer's disease
US20080050367A1 (en) 1998-04-07 2008-02-28 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
US6750324B1 (en) 1997-12-02 2004-06-15 Neuralab Limited Humanized and chimeric N-terminal amyloid beta-antibodies
US6787523B1 (en) 1997-12-02 2004-09-07 Neuralab Limited Prevention and treatment of amyloidogenic disease
US6710226B1 (en) 1997-12-02 2004-03-23 Neuralab Limited Transgenic mouse assay to determine the effect of Aβ antibodies and Aβ Fragments on alzheimer's disease characteristics
US7179892B2 (en) 2000-12-06 2007-02-20 Neuralab Limited Humanized antibodies that recognize beta amyloid peptide
US6905686B1 (en) 1997-12-02 2005-06-14 Neuralab Limited Active immunization for treatment of alzheimer's disease
US7964192B1 (en) 1997-12-02 2011-06-21 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidgenic disease
US7588766B1 (en) 2000-05-26 2009-09-15 Elan Pharma International Limited Treatment of amyloidogenic disease
PT1659179E (pt) 1998-02-05 2011-09-16 Glaxosmithkline Biolog Sa Derivados de antigénios associados a tumor da família mage e sequências de ácidos nucleicos codificando-os, utilizados para a preparação de proteínas de fusão e de composições para vacinação
PL343429A1 (en) * 1998-03-09 2001-08-13 Smithkline Beecham Biolog Combined vaccine compositions
US20020147143A1 (en) 1998-03-18 2002-10-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
GB9806095D0 (en) * 1998-03-20 1998-05-20 Smithkline Beecham Biolog Novel compounds
IL138809A0 (en) 1998-04-07 2001-10-31 Corixa Corp Fusion proteins of mycobacterium tuberculosis antigens and pharmaceutical compositions containing the same
GB9808866D0 (en) 1998-04-24 1998-06-24 Smithkline Beecham Biolog Novel compounds
DK1075276T3 (da) * 1998-05-07 2008-02-11 Corixa Corp Adjuvanssammensætning og fremgangsmåder til dens anvendelse
US20030147882A1 (en) 1998-05-21 2003-08-07 Alan Solomon Methods for amyloid removal using anti-amyloid antibodies
US6306404B1 (en) 1998-07-14 2001-10-23 American Cyanamid Company Adjuvant and vaccine compositions containing monophosphoryl lipid A
PL346213A1 (en) 1998-08-07 2002-01-28 Univ Washington Immunological herpes simplex virus antigens and methods for use thereof
US6692752B1 (en) 1999-09-08 2004-02-17 Smithkline Beecham Biologicals S.A. Methods of treating human females susceptible to HSV infection
GB9819898D0 (en) * 1998-09-11 1998-11-04 Smithkline Beecham Plc New vaccine and method of use
GB9820525D0 (en) 1998-09-21 1998-11-11 Allergy Therapeutics Ltd Formulation
US20030235557A1 (en) 1998-09-30 2003-12-25 Corixa Corporation Compositions and methods for WT1 specific immunotherapy
GB9822714D0 (en) 1998-10-16 1998-12-09 Smithkline Beecham Sa Vaccines
CN100406060C (zh) * 1998-10-16 2008-07-30 史密丝克莱恩比彻姆生物有限公司 一种佐剂组合物
EP2277893A3 (en) 1998-12-08 2011-03-30 Corixa Corporation Compounds and methods for treatment and diagnosis of chlamydial infection
EP2374889A3 (en) 1998-12-08 2012-02-22 GlaxoSmithKline Biologicals SA Novel compounds
US20020119158A1 (en) 1998-12-17 2002-08-29 Corixa Corporation Compositions and methods for the therapy and diagnosis of ovarian cancer
US6579973B1 (en) 1998-12-28 2003-06-17 Corixa Corporation Compositions for the treatment and diagnosis of breast cancer and methods for their use
US7198920B1 (en) 1999-01-29 2007-04-03 Corika Corporation HER-2/neu fusion proteins
US20040006242A1 (en) 1999-02-01 2004-01-08 Hawkins Lynn D. Immunomodulatory compounds and method of use thereof
EP1147117B1 (en) * 1999-02-01 2004-06-16 Eisai Co., Ltd. Immunological adjuvant compounds
US7915238B2 (en) * 1999-02-01 2011-03-29 Eisai R & D Management Co., Ltd. Immunomodulatory compounds and methods of use thereof
US6835721B2 (en) * 1999-02-01 2004-12-28 Eisai Co., Ltd. Immunomodulatory compounds and methods of use thereof
US6551600B2 (en) 1999-02-01 2003-04-22 Eisai Co., Ltd. Immunological adjuvant compounds compositions and methods of use thereof
GB2348132B (en) * 1999-03-02 2004-08-04 Nedaa Abdul-Ghani Nasif Asthma/allergy therapy that targets t-lymphocytes and/or eosinophils
CA2366147A1 (en) 1999-03-11 2000-09-14 Smithkline Beecham Biologicals S.A. Casb618 polynucleotides and polypeptides and their use
AU3164600A (en) 1999-03-12 2000-10-04 Smithkline Beecham Biologicals (Sa) Novel compounds
DE122009000054I1 (de) 1999-03-19 2009-12-31 Glaxosmithkline Biolog Sa Impfstoff gegen bakterielle antigene
GB9909077D0 (en) 1999-04-20 1999-06-16 Smithkline Beecham Biolog Novel compositions
MXPA01009688A (es) * 1999-03-26 2002-03-27 Smithkline Beecham Biolog Compuestos novedosos.
ATE399793T1 (de) 1999-04-02 2008-07-15 Corixa Corp Verbindungen und verfahren für therapie und diagnose von lungenkrebs
CN1227030C (zh) 1999-04-19 2005-11-16 史密丝克莱恩比彻姆生物有限公司 包含皂甙和免疫刺激寡核苷酸的佐剂组合物
US6558670B1 (en) 1999-04-19 2003-05-06 Smithkline Beechman Biologicals S.A. Vaccine adjuvants
GB9908885D0 (en) * 1999-04-19 1999-06-16 Smithkline Beecham Biolog Vccine
BR0010539A (pt) * 1999-05-13 2002-02-19 American Cyanamid Co Composição antigênica, e, método para incrementar a capacidade de uma composição antigênica
US6787637B1 (en) 1999-05-28 2004-09-07 Neuralab Limited N-Terminal amyloid-β antibodies
UA81216C2 (en) 1999-06-01 2007-12-25 Prevention and treatment of amyloid disease
US6635261B2 (en) 1999-07-13 2003-10-21 Wyeth Holdings Corporation Adjuvant and vaccine compositions containing monophosphoryl lipid A
GB9918319D0 (en) 1999-08-03 1999-10-06 Smithkline Beecham Biolog Vaccine composition
GB9921146D0 (en) * 1999-09-07 1999-11-10 Smithkline Beecham Biolog Novel composition
GB9921147D0 (en) * 1999-09-07 1999-11-10 Smithkline Beecham Biolog Novel composition
GB9923176D0 (en) * 1999-09-30 1999-12-01 Smithkline Beecham Biolog Novel composition
EP1227837B1 (en) 1999-10-22 2008-05-21 Aventis Pasteur Limited Method of inducing and/or enhancing an immune response to tumor antigens
GB0000891D0 (en) * 2000-01-14 2000-03-08 Allergy Therapeutics Ltd Formulation
WO2001062778A2 (en) 2000-02-23 2001-08-30 Smithkline Beecham Biologicals S.A. Tumour-specific animal proteins
US20040002068A1 (en) 2000-03-01 2004-01-01 Corixa Corporation Compositions and methods for the detection, diagnosis and therapy of hematological malignancies
ATE398463T1 (de) * 2000-04-13 2008-07-15 Corixa Corp Immunostimulierende zusammnensetzungen die aminoalkyl glucosaminidephosphat und qs-21 enthalten
CA2407114A1 (en) 2000-04-21 2001-11-01 Corixa Corporation Compounds and methods for treatment and diagnosis of chlamydial infection
ATE513913T1 (de) 2000-05-10 2011-07-15 Sanofi Pasteur Ltd Durch mage minigene kodierte immunogene polypeptide und ihre verwendungen
AU2001268472A1 (en) * 2000-06-16 2002-01-02 Smith Kline Beecham Corporation Icp27-binding polynucleotides
DK2133100T3 (da) 2000-06-20 2012-01-23 Corixa Corp MTB32A-Antigen af Mycobacterium tuberculosis med inaktiveret aktivt sted og fusionsproteiner deraf
EP1319069B1 (en) 2000-06-28 2008-05-21 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
GB0108364D0 (en) 2001-04-03 2001-05-23 Glaxosmithkline Biolog Sa Vaccine composition
DZ3399A1 (fr) 2000-06-29 2002-01-03 Smithkline Beecham Biolog Composition de vaccin polyvalent
DE60115051T2 (de) 2000-07-31 2006-08-24 Eisai Co., Ltd. Immunologische adjuvans verbindungen
US7229623B1 (en) 2000-08-03 2007-06-12 Corixa Corporation Her-2/neu fusion proteins
UA79735C2 (uk) 2000-08-10 2007-07-25 Глаксосмітклайн Байолоджікалз С.А. Очищення антигенів вірусу гепатиту b (hbv) для використання у вакцинах
GB0022742D0 (en) 2000-09-15 2000-11-01 Smithkline Beecham Biolog Vaccine
GB0025577D0 (en) * 2000-10-18 2000-12-06 Smithkline Beecham Biolog Vaccine
PT1326638E (pt) 2000-10-18 2008-02-06 Glaxosmithkline Biolog Sa Vacinas contra cancros
EP1201250A1 (en) * 2000-10-25 2002-05-02 SMITHKLINE BEECHAM BIOLOGICALS s.a. Immunogenic compositions comprising liver stage malarial antigens
NZ594877A (en) 2000-10-27 2012-07-27 Novartis Vaccines & Diagnostic Nucleic acids and proteins from streptococcus groups A & B
US20040220076A1 (en) * 2000-11-16 2004-11-04 Laure Aurelian Prevention of recurrent viral disease
PE20020574A1 (es) 2000-12-06 2002-07-02 Wyeth Corp Anticuerpos humanizados que reconocen el peptido amiloideo beta
WO2002046477A2 (en) 2000-12-07 2002-06-13 Chiron Corporation Endogenous retroviruses up-regulated in prostate cancer
AU2002343321A1 (en) * 2001-01-26 2003-01-21 Walter Reed Army Institute Of Research Isolation and purification of plasmodium falciparum merozoite protein-142
US7306806B2 (en) 2001-01-26 2007-12-11 United States Of America As Represented By The Secretary Of The Army Recombinant P. falciparum merozoite protein-142 vaccine
GB0103171D0 (en) 2001-02-08 2001-03-28 Smithkline Beecham Biolog Vaccine composition
ATE503493T1 (de) 2001-02-23 2011-04-15 Glaxosmithkline Biolog Sa Influenza vakzinzusammensetzungen zur intradermaler verabreichung
US20030031684A1 (en) 2001-03-30 2003-02-13 Corixa Corporation Methods for the production of 3-O-deactivated-4'-monophosphoryl lipid a (3D-MLA)
GB0109297D0 (en) 2001-04-12 2001-05-30 Glaxosmithkline Biolog Sa Vaccine
JP2005504513A (ja) 2001-05-09 2005-02-17 コリクサ コーポレイション 前立腺癌の治療及び診断のための組成物及び方法
US20100221284A1 (en) 2001-05-30 2010-09-02 Saech-Sisches Serumwerk Dresden Novel vaccine composition
TWI228420B (en) 2001-05-30 2005-03-01 Smithkline Beecham Pharma Gmbh Novel vaccine composition
GB0115176D0 (en) 2001-06-20 2001-08-15 Chiron Spa Capular polysaccharide solubilisation and combination vaccines
AU2002354644C1 (en) 2001-07-10 2009-04-30 Corixa Corporation Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres
GB0118249D0 (en) 2001-07-26 2001-09-19 Chiron Spa Histidine vaccines
CN1561230B (zh) * 2001-07-26 2011-09-07 奥塔戈创新公司 抗原组合物
GB0118367D0 (en) 2001-07-27 2001-09-19 Glaxosmithkline Biolog Sa Novel use
GB0121591D0 (en) 2001-09-06 2001-10-24 Chiron Spa Hybrid and tandem expression of neisserial proteins
US20030138434A1 (en) * 2001-08-13 2003-07-24 Campbell Robert L. Agents for enhancing the immune response
US7361352B2 (en) 2001-08-15 2008-04-22 Acambis, Inc. Influenza immunogen and vaccine
AR045702A1 (es) 2001-10-03 2005-11-09 Chiron Corp Composiciones de adyuvantes.
DK1581119T3 (da) 2001-12-17 2013-05-13 Corixa Corp Sammensætninger og fremgangsmåder til terapi og diagnose af inflammatoriske tarmsygdomme
US7030094B2 (en) * 2002-02-04 2006-04-18 Corixa Corporation Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and QS-21
WO2003070909A2 (en) 2002-02-20 2003-08-28 Chiron Corporation Microparticles with adsorbed polypeptide-containing molecules
US7351413B2 (en) 2002-02-21 2008-04-01 Lorantis, Limited Stabilized HBc chimer particles as immunogens for chronic hepatitis
MY139983A (en) 2002-03-12 2009-11-30 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
GB0206360D0 (en) 2002-03-18 2002-05-01 Glaxosmithkline Biolog Sa Viral antigens
US20030224013A1 (en) * 2002-04-19 2003-12-04 Cole Garry T. Methods for protection against Coccidioides spp. infection using Coccidioides spp. urea amidohydrolase (Ure) protein
EP2330113B1 (en) 2002-04-19 2016-06-29 The Governing Council Of The University Of Toronto Immunological methods and compositions for the treatment of Alzheimer's disease
ATE545651T1 (de) 2002-06-13 2012-03-15 Novartis Vaccines & Diagnostic Vektoren zur expression von hml-2-polypeptiden
US7078041B2 (en) 2002-07-18 2006-07-18 University Of Washington Rapid, efficient purification of HSV-specific T-lymphocytes and HSV antigens identified via same
JP4726485B2 (ja) * 2002-08-02 2011-07-20 大日本住友製薬株式会社 細菌細胞壁骨格成分製剤
CA2493977A1 (en) 2002-08-02 2004-02-19 Glaxosmithkline Biologicals Sa Vaccine composition comprising lipooligosaccharide with reduced phase variability
GB0220194D0 (en) 2002-08-30 2002-10-09 Chiron Spa Improved vesicles
EP2351579B1 (en) 2002-10-11 2016-09-21 Novartis Vaccines and Diagnostics S.r.l. Polypeptide vaccines for broad protection against hypervirulent meningococcal lineages
CA2502268A1 (en) 2002-10-23 2004-05-06 Glaxosmithkline Biologicals S.A. Methods for vaccinating against malaria
US20070059329A1 (en) 2002-11-15 2007-03-15 Nathalie Norais Unexpected surface proteins in meningococcus
GB0227346D0 (en) 2002-11-22 2002-12-31 Chiron Spa 741
US7858098B2 (en) 2002-12-20 2010-12-28 Glaxosmithkline Biologicals, S.A. Vaccine
EP1581812B1 (en) 2003-01-06 2008-07-16 Wyeth Compositions and methods for diagnosing and treating colon cancers
CN101926988B (zh) 2003-01-30 2014-06-04 诺华疫苗和诊断有限公司 抗多种脑膜炎球菌血清组的可注射性疫苗
CA2521051C (en) 2003-04-04 2012-03-20 Pfizer Products Inc. Microfluidized oil-in-water emulsions and vaccine compositions
GB0308198D0 (en) 2003-04-09 2003-05-14 Chiron Srl ADP-ribosylating bacterial toxin
US7731967B2 (en) * 2003-04-30 2010-06-08 Novartis Vaccines And Diagnostics, Inc. Compositions for inducing immune responses
ES2328697T5 (es) 2003-06-02 2017-07-25 Novartis Vaccines And Diagnostics, Inc. Composiciones inmunogénicas basadas en micropartículas que comprenden toxoide adsorbido y un antígeno que contiene un polisacárido
US20060035242A1 (en) 2004-08-13 2006-02-16 Michelitsch Melissa D Prion-specific peptide reagents
JP4738339B2 (ja) 2003-10-02 2011-08-03 ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル 複数の髄膜炎菌血清群についての液体ワクチン
AU2004277342B2 (en) 2003-10-02 2010-12-16 Glaxosmithkline Biologicals S.A. Pertussis antigens and use thereof in vaccination
GB0323103D0 (en) 2003-10-02 2003-11-05 Chiron Srl De-acetylated saccharides
ES2541779T3 (es) 2004-02-05 2015-07-24 The Ohio State University Research Foundation Péptidos VEGF quiméricos
WO2005107797A1 (en) 2004-03-09 2005-11-17 Chiron Corporation Influenza virus vaccines
EP1741438A4 (en) * 2004-04-22 2009-08-26 Dainippon Sumitomo Pharma Co PHARMACEUTICAL PREPARATION CONTAINING SKELETAL COMPONENT OF BACTERIAL CELL WALL
GB0409745D0 (en) 2004-04-30 2004-06-09 Chiron Srl Compositions including unconjugated carrier proteins
GB0500787D0 (en) 2005-01-14 2005-02-23 Chiron Srl Integration of meningococcal conjugate vaccination
NZ550533A (en) 2004-04-30 2010-02-26 Novartis Vaccines & Diagnostic Meningococcal conjugate vaccination comprising N. meningitidis and diphtheria toxin
GB0410866D0 (en) 2004-05-14 2004-06-16 Chiron Srl Haemophilius influenzae
EP2848692B1 (en) 2004-05-21 2017-08-16 Novartis Vaccines and Diagnostics, Inc. Alphavirus vectors for influenza virus vaccines
CA2837748C (en) 2004-05-25 2016-03-08 Oregon Health And Science University Siv and hiv vaccination using rhcmv-and hcmv-based vaccine vectors
JP2008500984A (ja) * 2004-05-28 2008-01-17 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 ヴィロソームとサポニンアジュバントを含むワクチン組成物
US7758866B2 (en) 2004-06-16 2010-07-20 Glaxosmithkline Biologicals, S.A. Vaccine against HPV16 and HPV18 and at least another HPV type selected from HPV 31, 45 or 52
US8085126B2 (en) * 2004-07-27 2011-12-27 Honeywell International Inc. Identification with RFID asset locator for entry authorization
US20090317420A1 (en) 2004-07-29 2009-12-24 Chiron Corporation Immunogenic compositions for gram positive bacteria such as streptococcus agalactiae
GB0417494D0 (en) 2004-08-05 2004-09-08 Glaxosmithkline Biolog Sa Vaccine
AU2005287505A1 (en) 2004-09-22 2006-03-30 Biosynexus Incorporated Staphylococcal immunogenic compositions
EP3312272B1 (en) 2004-10-08 2019-08-28 The Government of The United States of America as represented by The Secretary of The Department of Health and Human Services Modulation of replicative fitness by using less frequently used synonymous codons
GB0424092D0 (en) 2004-10-29 2004-12-01 Chiron Srl Immunogenic bacterial vesicles with outer membrane proteins
US7625560B2 (en) 2004-12-15 2009-12-01 Janssen Alzheimer Immunotherapy Humanized antibodies that recognize beta amyloid peptide
PE20061329A1 (es) 2004-12-15 2006-12-08 Neuralab Ltd Anticuerpos ab humanizados para mejorar la cognicion
CN101107007B (zh) 2005-01-27 2011-08-17 奥克兰儿童医院及研究中心 对脑膜炎奈瑟球菌所致疾病具有广谱保护作用的gna1870囊泡疫苗
GB0502095D0 (en) 2005-02-01 2005-03-09 Chiron Srl Conjugation of streptococcal capsular saccharides
GB0503337D0 (en) 2005-02-17 2005-03-23 Glaxosmithkline Biolog Sa Compositions
SG164344A1 (en) 2005-02-18 2010-09-29 Novartis Vaccines & Diagnostics Srl Immunogens from uropathogenic escherichia coli
DK2351772T3 (en) 2005-02-18 2016-09-05 Glaxosmithkline Biologicals Sa Proteins and nucleic acids from meningitis / sepsis-associated Escherichia coli
GB0504436D0 (en) 2005-03-03 2005-04-06 Glaxosmithkline Biolog Sa Vaccine
TW200700078A (en) * 2005-03-23 2007-01-01 Glaxosmithkline Biolog Sa Novel use
GB0506001D0 (en) * 2005-03-23 2005-04-27 Glaxosmithkline Biolog Sa Novel use
WO2006104890A2 (en) 2005-03-31 2006-10-05 Glaxosmithkline Biologicals Sa Vaccines against chlamydial infection
US20070292418A1 (en) * 2005-04-26 2007-12-20 Eisai Co., Ltd. Compositions and methods for immunotherapy
US7976852B2 (en) * 2005-04-26 2011-07-12 Eisai R&D Management Co., Ltd. Compositions and methods for cancer immunotherapy
KR20120089475A (ko) 2005-04-29 2012-08-10 인펙셔스 디지즈 리서치 인스티튜트 (아이디알아이) 결핵균 감염을 예방 또는 치료하기 위한 신규한 방법
AU2006261342B2 (en) 2005-06-15 2012-02-02 The Ohio State University Research Foundation Her-2 peptides
GB0513421D0 (en) 2005-06-30 2005-08-03 Glaxosmithkline Biolog Sa Vaccines
WO2007005627A2 (en) 2005-07-01 2007-01-11 Forsyth Dental Infirmary For Children Tuberculosis antigen detection assays and vaccines
US20070078376A1 (en) * 2005-09-30 2007-04-05 Smith Gregory A Functionalized microneedles transdermal drug delivery systems, devices, and methods
WO2007041314A2 (en) * 2005-09-30 2007-04-12 Tti Ellebeau, Inc. Transdermal drug delivery systems, devices, and methods employing novel pharmaceutical vehicles
KR20080066712A (ko) * 2005-09-30 2008-07-16 티티아이 엘뷰 가부시키가이샤 관능화된 미세바늘 경피 약물 전달 시스템, 장치 및 방법
GB0519871D0 (en) 2005-09-30 2005-11-09 Secr Defence Immunogenic agents
US20110223197A1 (en) 2005-10-18 2011-09-15 Novartis Vaccines And Diagnostics Inc. Mucosal and Systemic Immunization with Alphavirus Replicon Particles
US11707520B2 (en) 2005-11-03 2023-07-25 Seqirus UK Limited Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture
AU2006310163B2 (en) 2005-11-04 2011-09-15 Seqirus UK Limited Influenza vaccine with reduced amount of oil-in-water emulsion as adjuvant
NZ568210A (en) * 2005-11-04 2012-12-21 Novartis Vaccines & Diagnostic Emulsions with free aqueous-phase surfactant as adjuvants for split influenza vaccines
AU2006310337B9 (en) * 2005-11-04 2013-11-28 Novartis Ag Adjuvanted influenza vaccines including cytokine-inducing agents
PL1945252T3 (pl) 2005-11-04 2013-11-29 Seqirus Uk Ltd Szczepionki zawierające oczyszczone antygeny powierzchniowe otrzymane z wirusów grypy hodowanych w hodowli komórkowej i skwalen jako adiuwant
GB0522765D0 (en) 2005-11-08 2005-12-14 Chiron Srl Combination vaccine manufacture
CA2630218A1 (en) * 2005-11-18 2007-08-30 The Ohio State University Research Foundation Viral gene products and methods for vaccination to prevent viral associated diseases
CA2629193C (en) * 2005-11-18 2016-03-29 3M Innovative Properties Company Coatable compositions, coatings derived therefrom and microarrays having such coatings
EP2360175B1 (en) 2005-11-22 2014-07-16 Novartis Vaccines and Diagnostics, Inc. Norovirus and Sapovirus virus-like particles (VLPs)
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
TWI457133B (zh) * 2005-12-13 2014-10-21 Glaxosmithkline Biolog Sa 新穎組合物
PT1973564T (pt) 2005-12-22 2017-01-24 Glaxosmithkline Biologicals Sa Vacina compreendendo conjugados polissacarídicos capsulares de streptococcus pneumoniae
GB0607088D0 (en) 2006-04-07 2006-05-17 Glaxosmithkline Biolog Sa Vaccine
WO2007079190A2 (en) * 2005-12-29 2007-07-12 Tti Ellebeau, Inc. Device and method for enhancing immune response by electrical stimulation
US8617565B2 (en) 2006-01-17 2013-12-31 Arne Forsgren et al. Surface exposed Haemophilus influenzae protein (protein E; pE)
WO2007085969A2 (en) 2006-01-27 2007-08-02 Novartis Vaccines And Diagnostics Gmbh & Co Kg Influenza vaccines containing hemagglutinin and matrix proteins
US8173657B2 (en) 2006-03-23 2012-05-08 Novartis Ag Imidazoquinoxaline compounds as immunomodulators
US8063063B2 (en) 2006-03-23 2011-11-22 Novartis Ag Immunopotentiating compounds
CN101448523A (zh) 2006-03-24 2009-06-03 诺华疫苗和诊断有限两合公司 无需冷藏储存流感疫苗
BRPI0710210A2 (pt) 2006-03-30 2011-05-24 Glaxomithkline Biolog S A composição imunogênica, vacina, métodos para preparar a vacina, e para prevenir ou tratar infecção estafilocócica, uso da composição imunogênica, e, processo para conjugar oligassacarìdeo ou polissacarìdeo capsular
RU2561673C2 (ru) 2006-03-30 2015-08-27 Эмбрекс, Инк. Способы и композиции для вакцинации домашней птицы
US9839685B2 (en) 2006-04-13 2017-12-12 The Regents Of The University Of Michigan Methods of inducing human immunodeficiency virus-specific immune responses in a host comprising nasally administering compositions comprising a naonemulsion and recombinant GP120 immunogen
US10138279B2 (en) 2006-04-13 2018-11-27 Regents Of The University Of Michigan Compositions and methods for Bacillus anthracis vaccination
TW200806315A (en) 2006-04-26 2008-02-01 Wyeth Corp Novel formulations which stabilize and inhibit precipitation of immunogenic compositions
EP2390364A1 (en) 2006-06-02 2011-11-30 GlaxoSmithKline Biologicals S.A. Method for identifying whether a patient will be responder or not to immunotherapy based on the differnetial expression of the PRKCQ gene
US20100015168A1 (en) 2006-06-09 2010-01-21 Novartis Ag Immunogenic compositions for streptococcus agalactiae
EP2032161B1 (en) 2006-06-12 2012-07-11 GlaxoSmithKline Biologicals S.A. L3v los vaccines
US8153116B2 (en) 2006-07-11 2012-04-10 University Of Connecticut Use of conditional plasmodium strains lacking an essential gene in malaria vaccination
US8128921B2 (en) * 2006-07-11 2012-03-06 University Of Connecticut Use of conditional plasmodium strains lacking nutrient transporters in malaria vaccination
MX2009000660A (es) * 2006-07-17 2009-04-08 Glaxosmithkline Biolog Sa Vacuna de influenza.
PL2422810T3 (pl) 2006-07-17 2015-03-31 Glaxosmithkline Biologicals Sa Szczepionka przeciw grypie
WO2008009652A2 (en) 2006-07-18 2008-01-24 Glaxosmithkline Biologicals S.A. Vaccines for malaria
GB0614460D0 (en) 2006-07-20 2006-08-30 Novartis Ag Vaccines
WO2008012538A2 (en) 2006-07-25 2008-01-31 The Secretary Of State For Defence Live vaccine strains of francisella
US20100166788A1 (en) 2006-08-16 2010-07-01 Novartis Vaccines And Diagnostics Immunogens from uropathogenic escherichia coli
US9150619B2 (en) * 2006-09-01 2015-10-06 Csl Limited Method of elicting or inducing an immune response
US8956625B2 (en) 2006-09-07 2015-02-17 Glaxosmithkline Biologicals, S.A. Inactivated polio vaccines
JP5954921B2 (ja) 2006-09-11 2016-07-20 ノバルティス アーゲー 卵を使用しないインフルエンザウイルスワクチンの作製
EP2484375B1 (en) 2006-09-26 2018-05-23 Infectious Disease Research Institute Vaccine composition containing synthetic adjuvant
US20090181078A1 (en) 2006-09-26 2009-07-16 Infectious Disease Research Institute Vaccine composition containing synthetic adjuvant
PL2086582T3 (pl) 2006-10-12 2013-04-30 Glaxosmithkline Biologicals Sa Kompozycja zawierająca adiuwant w postaci emulsji typu olej w wodzie
WO2008043774A1 (en) * 2006-10-12 2008-04-17 Glaxosmithkline Biologicals S.A. Vaccine comprising an oil in water emulsion adjuvant
GB0622282D0 (en) 2006-11-08 2006-12-20 Novartis Ag Quality control methods
WO2008068631A2 (en) 2006-12-06 2008-06-12 Novartis Ag Vaccines including antigen from four strains of influenza virus
CN101675068A (zh) 2007-03-02 2010-03-17 葛兰素史密丝克莱恩生物有限公司 新的方法和组合物
US8486414B2 (en) 2007-04-04 2013-07-16 Infectious Disease Research Institute Immunogenic compositions comprising Mycobacterium tuberculosis polypeptides and fusions thereof
US9452209B2 (en) 2007-04-20 2016-09-27 Glaxosmithkline Biologicals Sa Influenza vaccine
CA2685506A1 (en) 2007-05-02 2008-11-13 Glaxosmithkline Biologicals S.A. Vaccine
GB0711858D0 (en) * 2007-06-19 2007-07-25 Glaxosmithkline Biolog Sa Vaccine
AU2008267208B2 (en) 2007-06-26 2012-01-19 Glaxosmithkline Biologicals S.A. Vaccine comprising streptococcus pneumoniae capsular polysaccharide conjugates
EA201070066A1 (ru) 2007-06-27 2010-06-30 Новартис Аг Вакцины против гриппа с низким содержанием добавок
GB0713880D0 (en) 2007-07-17 2007-08-29 Novartis Ag Conjugate purification
GB0714963D0 (en) 2007-08-01 2007-09-12 Novartis Ag Compositions comprising antigens
HUE025149T2 (hu) 2007-08-02 2016-01-28 Biondvax Pharmaceuticals Ltd Multimer multiepitóp influenza vakcinák
CN102027003A (zh) 2007-08-03 2011-04-20 哈佛大学校长及研究员协会 衣原体抗原
MX2010001752A (es) 2007-08-13 2010-03-10 Glaxosmithkline Biolog Sa Vacunas.
EP2197485B1 (en) 2007-09-12 2015-11-11 GlaxoSmithKline Biologicals SA Gas57 mutant antigens and gas57 antibodies
MX2010002965A (es) 2007-09-17 2010-09-14 Oncomethylome Sciences Sa Deteccion mejorada de la expresion de mage-a.
JO3076B1 (ar) 2007-10-17 2017-03-15 Janssen Alzheimer Immunotherap نظم العلاج المناعي المعتمد على حالة apoe
GB0810305D0 (en) 2008-06-05 2008-07-09 Novartis Ag Influenza vaccination
US8637053B2 (en) 2007-12-03 2014-01-28 President And Fellows Of Harvard College Chlamydia antigens
EP2227251A1 (en) 2007-12-06 2010-09-15 GlaxoSmithKline Biologicals SA Influenza composition
ES2664753T3 (es) * 2007-12-07 2018-04-23 Glaxosmithkline Biologicals Sa Composiciones de inducción de respuestas inmunes
WO2009117035A1 (en) 2007-12-19 2009-09-24 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Soluble forms of hendra and nipah virus f glycoprotein and uses thereof
GB0818453D0 (en) 2008-10-08 2008-11-12 Novartis Ag Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom
PL2235046T3 (pl) 2007-12-21 2012-12-31 Novartis Ag Zmutowane formy streptolizyny O
US8092813B1 (en) 2007-12-28 2012-01-10 Novartis Ag Polychlorinated biphenyls and squalene-containing adjuvants
WO2009104097A2 (en) 2008-02-21 2009-08-27 Novartis Ag Meningococcal fhbp polypeptides
AU2009223613B2 (en) 2008-03-10 2014-09-25 Children's Hospital & Research Center At Oakland Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use
US20110117131A1 (en) * 2008-04-09 2011-05-19 Ning Huang Production of OspA for Lyme Disease Control
BRPI0910963A2 (pt) * 2008-04-16 2016-01-05 Glaxosmithkline Biolog Sa composição imunogênica, método para tratar ou prevenir doença pneumocócica, e , uso de uma composição imunogênica
US9527906B2 (en) 2008-04-18 2016-12-27 The General Hospital Corporation Immunotherapies employing self-assembling vaccines
US9415006B2 (en) 2008-05-23 2016-08-16 The Regents Of The University Of Michigan Immunogenic compositions comprising nanoemulsion and hepatitis B virus immunogen and methods of using the same
US9114098B2 (en) 2008-06-04 2015-08-25 The Chemo-Sero-Therapeutic Research Institute Method for using inactivated Japanese encephalitis virus particles as adjuvant
CN102123724B (zh) 2008-06-19 2018-05-01 变异生技公司 治疗流行性感冒的组合物和方法
EP2318044B1 (en) 2008-08-01 2015-12-02 Gamma Vaccines Pty Limited Influenza vaccines
CA2735404C (en) 2008-08-28 2013-04-16 Novartis Ag Production of squalene from hyper-producing yeasts
GB0815872D0 (en) 2008-09-01 2008-10-08 Pasteur Institut Novel method and compositions
WO2010036945A2 (en) 2008-09-26 2010-04-01 The Regents Of The University Of Michigan Nanoemulsion therapeutic compositions and methods of using the same
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
US9974844B2 (en) 2008-11-17 2018-05-22 The Regents Of The University Of Michigan Cancer vaccine compositions and methods of using the same
GB0822001D0 (en) * 2008-12-02 2009-01-07 Glaxosmithkline Biolog Sa Vaccine
AU2009323682A1 (en) 2008-12-03 2010-06-10 Protea Vaccine Technologies Ltd. Glutamyl tRNA synthetase (GtS) fragments
PE20110891A1 (es) 2008-12-09 2011-12-23 Pfizer Vaccines Llc Vacuna de peptido ch3 de ige
CN107365751B (zh) 2008-12-16 2021-07-09 纳米医疗公司 流感疫苗的生产
AU2010204139A1 (en) 2009-01-12 2011-08-11 Novartis Ag Cna_B domain antigens in vaccines against gram positive bacteria
GB0900455D0 (en) 2009-01-13 2009-02-11 Secr Defence Vaccine
GB0901411D0 (en) 2009-01-29 2009-03-11 Secr Defence Treatment
GB0901423D0 (en) 2009-01-29 2009-03-11 Secr Defence Treatment
US20100234283A1 (en) 2009-02-04 2010-09-16 The Ohio State University Research Foundation Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use
US9278126B2 (en) 2009-02-10 2016-03-08 Seqirus UK Limited Influenza vaccines with reduced amounts of squalene
MX338898B (es) * 2009-02-17 2016-05-03 Glaxosmithkline Biolog Sa Vacuna contra el virus del dengue inactivado con un adyuvante libre de aluminio.
ES2733084T3 (es) 2009-03-06 2019-11-27 Glaxosmithkline Biologicals Sa Antígenos de Chlamydia
CN102575284A (zh) 2009-03-17 2012-07-11 MDx健康公司 改进的基因表达检测
SG175092A1 (en) 2009-04-14 2011-11-28 Novartis Ag Compositions for immunising against staphylococcus aerus
GB0906234D0 (en) 2009-04-14 2009-05-20 Secr Defence Vaccine
RU2536248C2 (ru) 2009-04-30 2014-12-20 Коули Фармасьютикал Груп, Инк. Пневмококковая вакцина и ее применения
WO2010132833A1 (en) 2009-05-14 2010-11-18 The Regents Of The University Of Michigan Streptococcus vaccine compositions and methods of using the same
WO2010136443A1 (en) 2009-05-27 2010-12-02 Glaxosmithkline Biologicals S.A. Casb7439 constructs
RU2732574C2 (ru) 2009-06-05 2020-09-21 Инфекшес Дизиз Рисерч Инститьют Синтетические глюкопиранозиллипидные адъюванты
EP2944320A1 (en) 2009-06-15 2015-11-18 National University of Singapore Influenza vaccine, composition, and methods of use
ES2566646T3 (es) 2009-06-16 2016-04-14 The Regents Of The University Of Michigan Vacunas en nanoemulsión
CA2803282C (en) 2009-07-06 2018-05-01 David E. Anderson Methods for preparing vesicles and formulations produced therefrom
US9849173B2 (en) 2009-07-06 2017-12-26 Variation Biotechnologies Inc. Methods for preparing vesicles and formulations produced therefrom
WO2011004263A2 (en) 2009-07-07 2011-01-13 Novartis Ag Conserved escherichia coli immunogens
ES2918381T3 (es) 2009-07-15 2022-07-15 Glaxosmithkline Biologicals Sa Composiciones de proteína F de VRS y métodos para producir las mismas
WO2011007257A1 (en) 2009-07-16 2011-01-20 Novartis Ag Detoxified escherichia coli immunogens
WO2011007961A2 (en) 2009-07-17 2011-01-20 Industry Academic Cooperation Foundation, Hallym University Immunostimulatory compositions comprising liposome-encapsulated oligonucleotides and epitpoes
KR20130127547A (ko) 2009-07-30 2013-11-22 화이자 백신스 엘엘씨 항원성 타우 펩타이드 및 이의 용도
GB0913680D0 (en) 2009-08-05 2009-09-16 Glaxosmithkline Biolog Sa Immunogenic composition
GB0913681D0 (en) 2009-08-05 2009-09-16 Glaxosmithkline Biolog Sa Immunogenic composition
EP2470204B1 (en) 2009-08-27 2015-12-16 GlaxoSmithKline Biologicals SA Hybrid polypeptides including meningococcal fhbp sequences
MX2012002639A (es) 2009-09-03 2012-03-14 Pfizer Vaccines Llc Vacuna de pcsk9.
NZ598645A (en) * 2009-09-10 2014-07-25 Merial Ltd New vaccine formulations comprising saponin-containing adjuvants
EP2475385A1 (en) 2009-09-10 2012-07-18 Novartis AG Combination vaccines against respiratory tract diseases
GB0917457D0 (en) 2009-10-06 2009-11-18 Glaxosmithkline Biolog Sa Method
GB0917003D0 (en) 2009-09-28 2009-11-11 Novartis Vaccines Inst For Global Health Srl Purification of bacterial vesicles
GB0917002D0 (en) 2009-09-28 2009-11-11 Novartis Vaccines Inst For Global Health Srl Improved shigella blebs
MX373250B (es) 2009-09-30 2020-05-04 Glaxosmithkline Biologicals S A Star Conjugación de polisacáridos capsulares de tipo 5 y de tipo 8 de staphylococcus aureus.
AU2010302344A1 (en) 2009-09-30 2012-04-26 Novartis Ag Expression of meningococcal fhbp polypeptides
RU2012117610A (ru) 2009-10-09 2013-11-20 СиБАЙО ЛИМИТЕД Варианты шаперонина 10
GB0918392D0 (en) 2009-10-20 2009-12-02 Novartis Ag Diagnostic and therapeutic methods
CN102917730A (zh) 2009-10-27 2013-02-06 诺华有限公司 修饰的脑膜炎球菌fHBP多肽
GB0918830D0 (en) 2009-10-27 2009-12-09 Glaxosmithkline Biolog Niederl Process
GB0919117D0 (en) 2009-10-30 2009-12-16 Glaxosmithkline Biolog Sa Process
GB0919690D0 (en) 2009-11-10 2009-12-23 Guy S And St Thomas S Nhs Foun compositions for immunising against staphylococcus aureus
WO2011067758A2 (en) 2009-12-02 2011-06-09 Protea Vaccine Technologies Ltd. Immunogenic fragments and multimers from streptococcus pneumoniae proteins
AU2010334428B2 (en) 2009-12-22 2015-05-21 Celldex Therapeutics, Inc. Vaccine compositions
WO2011087839A1 (en) 2009-12-22 2011-07-21 Baxter International Inc. Vaccine to influenza a virus
WO2011080595A2 (en) 2009-12-30 2011-07-07 Novartis Ag Polysaccharide immunogens conjugated to e. coli carrier proteins
EP2353609A1 (en) 2010-02-04 2011-08-10 Sanofi Pasteur Immunization compositions and methods
GB201003333D0 (en) 2010-02-26 2010-04-14 Novartis Ag Immunogenic proteins and compositions
GB201003924D0 (en) 2010-03-09 2010-04-21 Glaxosmithkline Biolog Sa Immunogenic composition
GB201003920D0 (en) 2010-03-09 2010-04-21 Glaxosmithkline Biolog Sa Method of treatment
JP2013521770A (ja) 2010-03-10 2013-06-13 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 ワクチン組成物
KR20130048208A (ko) 2010-03-11 2013-05-09 이뮨 디자인 코포레이션 인플루엔자 백신
EP2552480A1 (en) 2010-03-26 2013-02-06 GlaxoSmithKline Biologicals S.A. Hiv vaccine
ES2661569T3 (es) 2010-03-30 2018-04-02 Children's Hospital & Research Center At Oakland Proteínas de unión al factor H (fHbp) con propiedades alteradas y métodos de uso de las mismas
GB201005625D0 (en) 2010-04-01 2010-05-19 Novartis Ag Immunogenic proteins and compositions
WO2011127316A1 (en) 2010-04-07 2011-10-13 Novartis Ag Method for generating a parvovirus b19 virus-like particle
GB201006324D0 (en) 2010-04-15 2010-06-02 Glaxosmithkline Biolog Sa Vaccine
EP2575988A1 (en) 2010-05-28 2013-04-10 Tetris Online, Inc. Interactive hybrid asynchronous computer game infrastructure
DK2575870T3 (en) 2010-06-04 2017-02-13 Wyeth Llc vaccine Formulations
EP2575868A1 (en) 2010-06-07 2013-04-10 Pfizer Vaccines LLC Ige ch3 peptide vaccine
WO2011154863A1 (en) 2010-06-07 2011-12-15 Pfizer Inc. Her-2 peptides and vaccines
GB201009861D0 (en) 2010-06-11 2010-07-21 Novartis Ag OMV vaccines
US8658603B2 (en) 2010-06-16 2014-02-25 The Regents Of The University Of Michigan Compositions and methods for inducing an immune response
BR112013000394B8 (pt) 2010-07-06 2022-01-18 Variation Biotechnologies Inc Composição imunogênica, uso da mesma e método para preparar a referida composição
CN103154242B (zh) 2010-07-06 2015-09-30 诺华股份有限公司 诺如病毒衍生的免疫原性组合物和方法
US9192661B2 (en) 2010-07-06 2015-11-24 Novartis Ag Delivery of self-replicating RNA using biodegradable polymer particles
GB201015132D0 (en) 2010-09-10 2010-10-27 Univ Bristol Vaccine composition
GB201101665D0 (en) 2011-01-31 2011-03-16 Novartis Ag Immunogenic compositions
WO2012038801A1 (en) 2010-09-21 2012-03-29 National Institute Of Immunology A spray dried powder formulation for vaccines entrapping alum and the antigen in biodegradable polymer particles
US9168292B2 (en) 2010-09-27 2015-10-27 Crucell Holland B.V. Heterologous prime boost vaccination regimen against malaria
CA2812893A1 (en) 2010-09-27 2012-04-05 Glaxosmithkline Biologicals S.A. Vaccine
GB201017519D0 (en) 2010-10-15 2010-12-01 Novartis Vaccines Inst For Global Health S R L Vaccines
GB201101331D0 (en) 2011-01-26 2011-03-09 Glaxosmithkline Biolog Sa Compositions and uses
US20130345079A1 (en) 2010-10-27 2013-12-26 Infectious Disease Research Institute Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity
US20120114688A1 (en) 2010-11-08 2012-05-10 Infectious Disease Research Institute Vaccines comprising non-specific nucleoside hydrolase and sterol 24-c-methyltransferase (smt) polypeptides for the treatment and diagnosis of leishmaniasis
WO2012072769A1 (en) 2010-12-01 2012-06-07 Novartis Ag Pneumococcal rrgb epitopes and clade combinations
US9550811B2 (en) 2010-12-02 2017-01-24 Bionor Immuno As Peptide scaffold design
GB201022007D0 (en) 2010-12-24 2011-02-02 Imp Innovations Ltd DNA-sensor
US20130315959A1 (en) 2010-12-24 2013-11-28 Novartis Ag Compounds
EA034031B1 (ru) 2011-01-06 2019-12-20 Бионор Иммуно Ас Димерный пептид для индуцирования иммунного ответа против hiv и его применение
CN103501811B (zh) 2011-01-13 2016-03-30 变异生物技术公司 用于治疗病毒感染的组合物和方法
BR112013018074A2 (pt) 2011-01-13 2020-12-01 Variation Biotechnologies, Inc. métodos para a preparação de vesículas e formulações produzidas a partir dessas
LT2667892T (lt) 2011-01-26 2019-05-10 Glaxosmithkline Biologicals Sa Rsv imunizacijos režimas
WO2012100302A1 (en) 2011-01-27 2012-08-02 Gamma Vaccines Pty Limited Combination vaccines
CN103517713A (zh) 2011-02-22 2014-01-15 彼昂德瓦克斯医药有限公司 在改善的季节性和大流行性流感疫苗中的多聚体多表位多肽
WO2012131504A1 (en) 2011-03-02 2012-10-04 Pfizer Inc. Pcsk9 vaccine
ES2716010T3 (es) 2011-03-29 2019-06-07 Uab Research Foundation Métodos y composiciones para la proteína IL-10 de citomegalovirus
GB201106357D0 (en) 2011-04-14 2011-06-01 Pessi Antonello Composition and uses thereof
MX350795B (es) 2011-04-08 2017-09-19 Inmune Design Corp Composiciones inmunogenicas y metodos para utilizar las composiciones para inducir respuestas inmunes humorales y celulares.
TW201302779A (zh) 2011-04-13 2013-01-16 Glaxosmithkline Biolog Sa 融合蛋白質及組合疫苗
WO2012149307A2 (en) 2011-04-27 2012-11-01 Immune Design Corp. Synthetic long peptide (slp)-based vaccines
AU2012255971A1 (en) 2011-05-13 2013-05-02 Novartis Ag Pre-fusion RSV F antigens
CN103533953A (zh) 2011-05-17 2014-01-22 葛兰素史密丝克莱恩生物有限公司 针对肺炎链球菌的疫苗
CA2838188C (en) 2011-06-04 2017-04-18 Rochester General Hospital Research Institute Compositions and methods related to p6 of haemophilus influenzae
MX2013013627A (es) 2011-06-21 2014-04-25 Oncofactor Corp Composiciones y metodos para la terapia y diagnostico de cancer.
WO2013006569A2 (en) * 2011-07-01 2013-01-10 The Regents Of The University Of California Herpes virus vaccine and methods of use
WO2013016460A1 (en) 2011-07-25 2013-01-31 Novartis Ag Compositions and methods for assessing functional immunogenicity of parvovirus vaccines
GB201113570D0 (en) 2011-08-05 2011-09-21 Glaxosmithkline Biolog Sa Vaccine
CA2845872C (en) 2011-08-22 2023-03-28 Nanobio Corporation Herpes simplex virus nanoemulsion vaccine
GB201114923D0 (en) 2011-08-30 2011-10-12 Novartis Ag Immunogenic proteins and compositions
GB201114919D0 (en) 2011-08-30 2011-10-12 Glaxosmithkline Biolog Sa Method
CN104093421A (zh) 2011-09-09 2014-10-08 纳诺碧欧公司 纳米乳液呼吸道合胞病毒(rsv)亚单位疫苗
US9358284B2 (en) 2011-09-14 2016-06-07 Glaxosmithkline Biologicals Sa Methods for making saccharide-protein glycoconjugates
JP2014531442A (ja) 2011-09-14 2014-11-27 ノバルティス アーゲー Ｅｓｃｈｅｒｉｃｈｉａｃｏｌｉワクチンの組み合わせ
SI2758432T1 (sl) 2011-09-16 2019-07-31 Ucb Biopharma Sprl Nevtralizirajoča protitelesa proti glavnim eksotoksinom TCDA in TCDB iz clostridium difficile
EP2780034A1 (en) 2011-11-14 2014-09-24 Crucell Holland B.V. Heterologous prime-boost immunization using measles virus-based vaccines
US9902760B2 (en) 2011-11-23 2018-02-27 Bioven 3 Limited Recombinant proteins and their therapeutic uses
EP2788477A2 (en) 2011-12-07 2014-10-15 Institut Pasteur Identification of a swine parecho-like virus and applications
JP6084631B2 (ja) 2011-12-08 2017-02-22 ノバルティス アーゲー Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ毒素ベースのワクチン
AU2013208693B2 (en) 2012-01-12 2017-12-07 Variation Biotechnologies Inc. Compositions and methods for treating viral infections
WO2013108272A2 (en) 2012-01-20 2013-07-25 International Centre For Genetic Engineering And Biotechnology Blood stage malaria vaccine
EP2806894A4 (en) 2012-01-27 2015-11-04 Variation Biotechnologies Inc METHODS AND COMPOSITIONS FOR THERAPEUTIC AGENTS
CN110339160A (zh) 2012-02-07 2019-10-18 传染性疾病研究院 包含tlr4激动剂的改进佐剂制剂及其使用方法
MX2014010011A (es) 2012-02-24 2014-09-08 Novartis Ag Proteinas y composiciones de pilus.
US20130236484A1 (en) 2012-03-08 2013-09-12 Detectogen Inc. Leishmaniasis antigen detection assays and vaccines
JP6165231B2 (ja) 2012-03-23 2017-07-19 ピットニー・ファーマシューティカルズ・ピーティーワイ・リミテッド 癌の治療のためのキナーゼ阻害剤
GB201205189D0 (en) 2012-03-23 2012-05-09 Glaxosmithkline Biolog Sa Novel medical use
EP3492095A1 (en) 2012-04-01 2019-06-05 Technion Research & Development Foundation Limited Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies
CN104428312A (zh) 2012-04-02 2015-03-18 北卡罗来纳-查佩尔山大学 用于登革病毒表位的方法和组合物
KR102139959B1 (ko) 2012-04-26 2020-08-04 노파르티스 아게 항원 및 항원 조합물
US10279026B2 (en) 2012-04-26 2019-05-07 Glaxosmithkline Biologicals Sa Antigens and antigen combinations
EP2659908A1 (en) 2012-05-01 2013-11-06 Affiris AG Compositions
EP2659907A1 (en) 2012-05-01 2013-11-06 Affiris AG Compositions
EP2659906A1 (en) 2012-05-01 2013-11-06 Affiris AG Compositions
KR102125658B1 (ko) 2012-05-04 2020-06-22 화이자 인코포레이티드 전립선 관련된 항원 및 백신 기재 면역치료 요법
DK2850431T3 (en) 2012-05-16 2018-07-16 Immune Design Corp Vaccines against HSV-2
WO2013174832A1 (en) 2012-05-22 2013-11-28 Novartis Ag Meningococcus serogroup x conjugate
EP2666785A1 (en) 2012-05-23 2013-11-27 Affiris AG Complement component C5a-based vaccine
IN2014DN10408A (zh) 2012-06-05 2015-08-14 Univ Australian
BR112014030466A2 (pt) 2012-06-06 2017-09-12 Bionor Immuno As peptídeos derivados de proteínas virais para uso como imunógenos e reagentes de dosagem
KR20200067938A (ko) 2012-07-24 2020-06-12 사노피 파스퇴르 백신 조성물
KR20150036593A (ko) 2012-07-24 2015-04-07 사노피 파스퇴르 뎅기열 바이러스 감염 예방용 백신 조성물
EA031453B1 (ru) 2012-08-01 2019-01-31 Бавариан Нордик А/С Рекомбинантный модифицированный вирус осповакцины анкара (mva) и его применение
HUE065746T2 (hu) 2012-08-03 2024-06-28 Access To Advanced Health Inst Készítmények és eljárások aktív mycobacterium tuberculosis fertõzés kezelésére
CA2881325C (en) 2012-08-06 2020-09-29 Pitney Pharmaceuticals Pty Limited Compounds for the treatment of mtor pathway related diseases
JP2014040396A (ja) * 2012-08-23 2014-03-06 Chemo-Sero-Therapeutic Research Institute 脂質異常症治療薬を含有するアジュバント組成物
EP2703483A1 (en) 2012-08-29 2014-03-05 Affiris AG PCSK9 peptide vaccine
WO2014043189A1 (en) 2012-09-14 2014-03-20 The Regents Of The University Of Colorado, A Body Corporate Conditionally replication deficient herpes viruses and use thereof in vaccines
EP4056198A3 (en) 2012-09-18 2022-12-07 GlaxoSmithKline Biologicals SA Outer membrane vesicles
CA2885625A1 (en) 2012-10-02 2014-04-10 Glaxosmithkline Biologicals S.A. Nonlinear saccharide conjugates
AR092897A1 (es) 2012-10-03 2015-05-06 Novartis Ag Composiciones inmunogenicas
KR101819803B1 (ko) 2012-10-24 2018-01-17 플레이틀렛 타게티드 테라퓨틱스, 엘엘씨 혈소판 표적화 치료
AU2013351182C1 (en) 2012-11-30 2018-11-08 Glaxosmithkline Biologicals Sa Pseudomonas antigens and antigen combinations
BR112015012515B1 (pt) 2012-11-30 2023-04-11 Sanofi Pasteur Uso de antígenos, construções de ácido nucleico ou vetores virais capazes de expressar uma partícula do tipo vírus (vlp) da dengue e de uma vacina contra sarampo, uma vacina contra caxumba e uma vacina contra rubéola
LT3513806T (lt) 2012-12-05 2023-04-11 Glaxosmithkline Biologicals Sa Imunogeninė kompozicija
JP6502853B2 (ja) 2012-12-17 2019-04-17 ニューサウス イノベイションズ ピーティーワイ リミテッド ムチンが関与する疾患の処置
NZ629700A (en) 2012-12-24 2017-01-27 Cell Ideas Pty Ltd Vaccines for the treatment of cancer and compositions for enhancing vaccine efficacy
EP4272750A3 (en) 2013-02-07 2024-01-24 Children's Medical Center, Corp. Protein antigens that provide protection against pneumococcal colonization and/or disease
KR102391734B1 (ko) 2013-03-15 2022-04-29 인3바이오 리미티드 자기조립형 합성 단백질
ES2728865T3 (es) 2013-03-28 2019-10-29 Infectious Disease Res Inst Vacunas que comprenden polipéptidos de Leishmania para el tratamiento y el diagnóstico de la leishmaniasis
EA032326B1 (ru) 2013-04-18 2019-05-31 Иммьюн Дизайн Корп. Монотерапия gla для применения в лечении рака
ES2882374T3 (es) 2013-05-08 2021-12-01 Pharmgate Biologics Inc Vacuna para PCV2 y micoplasma
US20210145963A9 (en) 2013-05-15 2021-05-20 The Governors Of The University Of Alberta E1e2 hcv vaccines and methods of use
US9463198B2 (en) 2013-06-04 2016-10-11 Infectious Disease Research Institute Compositions and methods for reducing or preventing metastasis
GB201310008D0 (en) 2013-06-05 2013-07-17 Glaxosmithkline Biolog Sa Immunogenic composition for use in therapy
EP3590955A1 (en) 2013-06-26 2020-01-08 The University of North Carolina at Chapel Hill Methods and compositions for dengue virus vaccines
US10364277B2 (en) 2013-07-01 2019-07-30 Newsouth Innovations Pty Limited Diagnosis and treatment of autoimmune diseases
WO2015028478A1 (en) 2013-08-28 2015-03-05 Glaxosmithkline Biologicals S.A. Novel influenza antigens and antibodies
CN104436157A (zh) 2013-09-23 2015-03-25 恩金生物有限公司 流感疫苗和治疗
JP6306700B2 (ja) 2013-11-01 2018-04-04 ユニバーシティ オブ オスロＵｎｉｖｅｒｓｉｔｙ ｏｆ Ｏｓｌｏ アルブミン改変体及びその使用
EP3068426B1 (en) 2013-11-13 2020-02-12 University Of Oslo Outer membrane vesicles and uses thereof
WO2015071763A2 (en) 2013-11-15 2015-05-21 Oslo Universitetssykehus Hf Ctl peptide epitopes and antigen-specific t cells, methods for their discovery, and uses thereof
EP3071228A2 (en) 2013-11-20 2016-09-28 La Jolla Institute for Allergy and Immunology Pan pollen immunogens and methods and uses thereof for immune response modulation
WO2015077442A2 (en) 2013-11-20 2015-05-28 La Jolla Institute For Allergy And Immunology Grass pollen immunogens and methods and uses for immune response modulation
WO2015092710A1 (en) 2013-12-19 2015-06-25 Glaxosmithkline Biologicals, S.A. Contralateral co-administration of vaccines
EP3089754B1 (en) 2013-12-31 2021-04-21 Infectious Disease Research Institute Single vial vaccine formulations
WO2015103104A1 (en) 2014-01-06 2015-07-09 The United States Of America, As Represented By The Secretary Of Agriculture Attenuated salmonella enterica
EP3607966A1 (en) 2014-01-21 2020-02-12 Pfizer Inc Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
MA39228A1 (fr) 2014-01-21 2017-06-30 Immune Design Corp Compositions à utiliser pour le traitement d'états allergiques
US11160855B2 (en) 2014-01-21 2021-11-02 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
EP3104877B1 (en) 2014-02-11 2020-01-22 The USA, as represented by The Secretary, Department of Health and Human Services Pcsk9 vaccine and methods of using the same
TW201620927A (zh) 2014-02-24 2016-06-16 葛蘭素史密斯克藍生物品公司 Ｕｓｐａ２蛋白質構築體及其用途
WO2015131053A1 (en) 2014-02-28 2015-09-03 Alk-Abelló A/S Polypeptides derived from phl p and methods and uses thereof for immune response modulation
CA2944768C (en) 2014-04-03 2022-08-30 Biondvax Pharmaceuticals Ltd. Compositions of multimeric-multiepitope influenza polypeptides and their production
SMT202100116T1 (it) 2014-05-28 2021-05-07 Agenus Inc Anticorpi anti-gitr e metodi di utilizzo degli stessi
TW201623329A (zh) 2014-06-30 2016-07-01 亞佛瑞司股份有限公司 針對骨調素截斷變異體的疫苗及單株抗體暨其用途
US10759836B2 (en) 2014-07-18 2020-09-01 University Of Washington Cancer vaccine compositions and methods of use thereof
AR101256A1 (es) 2014-07-21 2016-12-07 Sanofi Pasteur Composición vacunal que comprende ipv y ciclodextrinas
CN106715464B (zh) 2014-07-23 2021-03-16 奥克兰儿童医院及研究中心 因子h结合蛋白变体及其使用方法
EP3204039B1 (en) 2014-10-10 2022-06-08 The Regents Of The University Of Michigan Nanoemulsion compositions for preventing, suppressing or eliminating allergic and inflammatory disease
AU2015338859A1 (en) 2014-11-02 2017-06-01 The University Of North Carolina At Chapel Hill Methods and compositions for recombinant dengue viruses for vaccine and diagnostic development
AR102548A1 (es) 2014-11-07 2017-03-08 Takeda Vaccines Inc Vacunas contra la enfermedad de manos, pies y boca y métodos de fabricación y uso
MA40920A (fr) 2014-11-07 2017-09-12 Takeda Vaccines Inc Vaccins de la main, du pied et de la bouche, et procédés de fabrication et d'utilisation de ceux-ci
MX387007B (es) 2014-12-10 2025-03-19 Glaxosmithkline Biologicals Sa Una composición inmunogénica para usarse en el tratamiento o prevención de la infección por staphylococcus aureus.
HK1245280A1 (zh) 2015-01-06 2018-08-24 Immunovaccine Technologies Inc. 脂质a模拟物、其制备方法和用途
FI3244917T3 (fi) 2015-01-15 2023-05-25 Pfizer Immunogeenisiä koostumuksia pneumokokkirokotteissa käytettäväksi
EP3258961A4 (en) 2015-02-20 2018-08-22 Board of Regents, The University of Texas System Methods and compositions for attenuated chlamydia as vaccine and vector
EP3268034A4 (en) 2015-03-05 2018-11-14 Northwestern University Non-neuroinvasive viruses and uses thereof
WO2016154010A1 (en) 2015-03-20 2016-09-29 Makidon Paul Immunogenic compositions for use in vaccination against bordetella
WO2016149771A1 (en) 2015-03-26 2016-09-29 Gamma Vaccines Pty Limited Streptococcal vaccine
BR112017025316A2 (en) 2015-05-26 2018-07-31 Ohio State Innovation Foundation swine flu virus nanoparticle-based vaccine strategy
US10576131B2 (en) 2015-06-03 2020-03-03 Affiris Ag IL-23-p19 vaccines
JP2018524323A (ja) 2015-06-26 2018-08-30 セキラス ユーケー リミテッド 抗原がマッチしたインフルエンザワクチン
CN107849119A (zh) 2015-07-07 2018-03-27 阿费里斯股份公司 用于治疗和预防IgE介导的疾病的疫苗
KR102225282B1 (ko) 2015-07-21 2021-03-10 화이자 인코포레이티드 접합된 캡슐형 사카라이드 항원을 포함하는 면역원성 조성물, 그를 포함하는 키트 및 그의 용도
HK1248531A1 (zh) 2015-08-25 2018-10-19 巴比塔‧阿格拉沃尔 免疫调节组合物及其使用方法
WO2017040790A1 (en) 2015-09-01 2017-03-09 Agenus Inc. Anti-pd-1 antibodies and methods of use thereof
ES2607715B1 (es) 2015-10-01 2018-01-17 Solutex Na, Lcc Proceso para la preparación y estabilización de emulsiones con omega-3 mediante redes cristalinas isométricas de derivados de celulosa
CN117229414A (zh) 2015-10-08 2023-12-15 艾伯塔大学理事会 丙型肝炎病毒e1/e2异二聚体及其生产方法
GB201518684D0 (en) 2015-10-21 2015-12-02 Glaxosmithkline Biolog Sa Vaccine
GB201518668D0 (en) 2015-10-21 2015-12-02 Glaxosmithkline Biolog Sa Immunogenic Comosition
WO2017085586A1 (en) 2015-11-20 2017-05-26 Pfizer Inc. Immunogenic compositions for use in pneumococcal vaccines
TW202134282A (zh) 2015-12-02 2021-09-16 美商艾吉納斯公司 抗體和使用彼之方法
WO2017109698A1 (en) 2015-12-22 2017-06-29 Glaxosmithkline Biologicals Sa Immunogenic formulation
MX2018008797A (es) 2016-01-19 2018-11-29 Pfizer Vacunas contra el cancer.
GB201603625D0 (en) 2016-03-02 2016-04-13 Glaxosmithkline Biolog Sa Novel influenza antigens
US20170260286A1 (en) 2016-03-10 2017-09-14 The General Hospital Corporation Antigen-Binding Fusion Proteins with Modified HSP70 Domains
EP4659813A2 (en) 2016-03-14 2025-12-10 Universitetet I Oslo Engineered immunoglobulins with altered fcrn binding
WO2017158421A1 (en) 2016-03-14 2017-09-21 University Of Oslo Anti-viral engineered immunoglobulins
WO2017167768A1 (en) 2016-03-28 2017-10-05 Glaxosmithkline Biologicals S.A. Novel vaccine composition
BR112018073690B1 (pt) 2016-05-16 2022-05-24 Infectious Disease Research Institute Formulação contendo agonista de tlr e métodos de uso
WO2017201390A1 (en) 2016-05-19 2017-11-23 The Regents Of The University Of Michigan Novel adjuvant compositions
WO2017205225A2 (en) 2016-05-21 2017-11-30 Infectious Disease Research Institute Compositions and methods for treating secondary tuberculosis and nontuberculous mycobacterium infections
CA3024508A1 (en) 2016-05-27 2017-11-30 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
MX393217B (es) 2016-06-01 2025-03-11 Infectious Disease Res Inst Particulas de nanoalumbre que contienen un agente de dimensionamiento
GB201610599D0 (en) 2016-06-17 2016-08-03 Glaxosmithkline Biologicals Sa Immunogenic Composition
US11780924B2 (en) 2016-06-21 2023-10-10 University Of Oslo HLA binding vaccine moieties and uses thereof
US11498956B2 (en) 2016-08-23 2022-11-15 Glaxosmithkline Biologicals Sa Fusion peptides with antigens linked to short fragments of invariant chain(CD74)
GB201614799D0 (en) 2016-09-01 2016-10-19 Glaxosmithkline Biologicals Sa Compositions
CA3036218A1 (en) 2016-09-16 2018-03-22 Infectious Disease Research Institute Vaccines comprising mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy
WO2018060288A1 (en) 2016-09-29 2018-04-05 Glaxosmithkline Biologicals S.A. Compositions and methods of treatment of persistent hpv infection
TWI773694B (zh) 2016-10-11 2022-08-11 美商艾吉納斯公司 抗ｌａｇ－３抗體及其使用方法
WO2018096396A1 (en) 2016-11-22 2018-05-31 University Of Oslo Albumin variants and uses thereof
GB201620968D0 (en) 2016-12-09 2017-01-25 Glaxosmithkline Biologicals Sa Adenovirus polynucleotides and polypeptides
KR20190103226A (ko) 2017-01-13 2019-09-04 아게누스 인코포레이티드 Ny-eso-1에 결합하는 t 세포 수용체 및 이의 사용 방법
SI3570879T1 (sl) 2017-01-20 2022-06-30 Pfizer Inc. Imunogenska kompozicija za uporabo v pnevmokoknih cepivih
CA3057171A1 (en) 2017-03-30 2018-10-04 The University Of Queensland Chimeric polypeptides containing virus fusion ectodomain and complementary heptad repeats and uses thereof
WO2018178265A1 (en) 2017-03-31 2018-10-04 Glaxosmithkline Intellectual Property Development Limited Immunogenic composition, use and method of treatment
WO2018178264A1 (en) 2017-03-31 2018-10-04 Glaxosmithkline Intellectual Property Development Limited Immunogenic composition, use and method of treatment
JP7297672B2 (ja) 2017-04-13 2023-06-26 アジェナス インコーポレイテッド 抗ｃｄ１３７抗体およびその使用方法
WO2018204363A1 (en) 2017-05-01 2018-11-08 Agenus Inc. Anti-tigit antibodies and methods of use thereof
CA3066915A1 (en) 2017-06-11 2018-12-20 Molecular Express, Inc. Methods and compositions for substance use disorder vaccine formulations and uses thereof
EP3638207B1 (en) 2017-06-15 2024-12-18 Access to Advanced Health Institute Nanostructured lipid carriers and stable emulsions and uses thereof
JP7751357B2 (ja) 2017-07-18 2025-10-08 イン３バイオ・リミテッド 合成タンパク質およびその治療学的用途
CN110996994A (zh) 2017-08-14 2020-04-10 葛兰素史密丝克莱恩生物有限公司 加强免疫应答的方法
US11123415B2 (en) 2017-08-16 2021-09-21 Ohio State Innovation Foundation Nanoparticle compositions for Salmonella vaccines
WO2019046856A1 (en) 2017-09-04 2019-03-07 Agenus Inc. T-CELL RECEPTORS THAT BIND TO SPECIFIC PHOSPHOPEPTIDES OF MIXED LINEAR LEUKEMIA (MLL) AND METHODS OF USE THEREOF
US12268736B2 (en) 2017-09-07 2025-04-08 University Of Oslo Vaccine molecules
EP3678699A1 (en) 2017-09-07 2020-07-15 University Of Oslo Vaccine molecules
AU2018330165B2 (en) 2017-09-08 2025-07-17 Access To Advanced Health Institute Liposomal formulations comprising saponin and methods of use
WO2019079594A1 (en) 2017-10-18 2019-04-25 The University Of North Carolina At Chapel Hill METHODS AND COMPOSITIONS FOR VACCINES AGAINST NOVOVIRUS AND DIAGNOSIS OF NOVOVIRUS
CA3081578A1 (en) 2017-11-03 2019-05-09 Takeda Vaccines, Inc. Zika vaccines and immunogenic compositions, and methods of using the same
GB201721069D0 (en) 2017-12-15 2018-01-31 Glaxosmithkline Biologicals Sa Hepatitis B Immunisation regimen and compositions
GB201721068D0 (en) 2017-12-15 2018-01-31 Glaxosmithkline Biologicals Sa Hepatitis B immunisation regimen and compositions
GB201721576D0 (en) 2017-12-21 2018-02-07 Glaxosmithkline Biologicals Sa Hla antigens and glycoconjugates thereof
GB201721582D0 (en) 2017-12-21 2018-02-07 Glaxosmithkline Biologicals Sa S aureus antigens and immunogenic compositions
WO2019173438A1 (en) 2018-03-06 2019-09-12 Stc. Unm Compositions and methods for reducing serum triglycerides
MX2020013553A (es) 2018-06-12 2021-02-26 Glaxosmithkline Biologicals Sa Polinucleotidos y polipeptidos de adenovirus.
CA3107077A1 (en) 2018-08-07 2020-02-13 Glaxosmithkline Biologicals Sa Processes and vaccines
US20210220462A1 (en) 2018-08-23 2021-07-22 Glaxosmithkline Biologicals Sa Immunogenic proteins and compositions
US11260119B2 (en) 2018-08-24 2022-03-01 Pfizer Inc. Escherichia coli compositions and methods thereof
EP3843782A1 (en) 2018-08-29 2021-07-07 Centre Hospitalier Universitaire Vaudois (CHUV) Ebola vaccine compositions and methods of using same
US12239699B2 (en) 2018-09-11 2025-03-04 Shanghai Public Health Clinical Center Immunogen for broad-spectrum influenza vaccine and application thereof
WO2020115171A1 (en) 2018-12-06 2020-06-11 Glaxosmithkline Biologicals Sa Immunogenic compositions
JP7551618B2 (ja) 2018-12-12 2024-09-17 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 Ｏ－結合型グリコシル化のための修飾キャリアタンパク質
WO2020121159A1 (en) 2018-12-12 2020-06-18 Pfizer Inc. Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof
WO2020128012A1 (en) 2018-12-21 2020-06-25 Glaxosmithkline Biologicals Sa Methods of inducing an immune response
GB201901608D0 (en) 2019-02-06 2019-03-27 Vib Vzw Vaccine adjuvant conjugates
JP7239509B6 (ja) 2019-02-22 2023-03-28 ファイザー・インク 細菌多糖類を精製するための方法
CN113573730A (zh) 2019-03-05 2021-10-29 葛兰素史密斯克莱生物公司 乙型肝炎免疫方案和组合物
CA3136278A1 (en) 2019-04-10 2020-10-15 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof
US20220221455A1 (en) 2019-04-18 2022-07-14 Glaxosmithkline Biologicals Sa Antigen binding proteins and assays
US12318436B2 (en) 2019-05-25 2025-06-03 Access To Advanced Health Institute Composition and method for spray drying an adjuvant vaccine emulsion
KR20220058527A (ko) 2019-06-25 2022-05-09 인3바이오 리미티드 안정화된 키메라 합성 단백질 및 그 치료 용도
KR20220035457A (ko) 2019-07-21 2022-03-22 글락소스미스클라인 바이오로지칼즈 에스.에이. 치료 바이러스 백신
EP3770269A1 (en) 2019-07-23 2021-01-27 GlaxoSmithKline Biologicals S.A. Quantification of bioconjugate glycosylation
EP4010014A1 (en) 2019-08-05 2022-06-15 GlaxoSmithKline Biologicals S.A. Immunogenic composition
AU2020325279A1 (en) 2019-08-06 2022-03-17 The University Of North Carolina At Chapel Hill Methods and compositions for stabilized recombinant flavivirus E protein dimers
MX2022002315A (es) 2019-08-30 2022-03-25 Agenus Inc Anticuerpos anti-cd96 y sus metodos de uso.
EP3799884A1 (en) 2019-10-01 2021-04-07 GlaxoSmithKline Biologicals S.A. Immunogenic compositions
EP3808765A1 (en) 2019-10-14 2021-04-21 ETH Zurich Cell line for tcr discovery and engineering and methods of use thereof
MX2022005252A (es) 2019-11-01 2022-06-08 Pfizer Composiciones de escherichia coli y metodos de las mismas.
EP4058581A1 (en) 2019-11-15 2022-09-21 Infectious Disease Research Institute Rig-i agonist and adjuvant formulation for tumor treatment
NL2027383B1 (en) 2020-01-24 2022-04-06 Aim Immunotech Inc Methods, compositions, and vaccines for treating a virus infection
EP4103587A1 (en) 2020-02-14 2022-12-21 Immunor AS Corona virus vaccine
US20230085173A1 (en) 2020-02-21 2023-03-16 Pfizer Inc. Purification of saccharides
PE20230170A1 (es) 2020-02-23 2023-02-01 Pfizer Composiciones de escherichia coli y sus metodos
JP2023514825A (ja) 2020-02-26 2023-04-11 ヴェルシテック リミテッド コロナウイルス感染症に対するｐｄ－１ベースのワクチン
EP4132478A1 (en) 2020-04-09 2023-02-15 Finncure Oy Mimetic nanoparticles for preventing the spreading and lowering the infection rate of novel coronaviruses
US12194157B2 (en) 2020-04-09 2025-01-14 Finncure Oy Carrier for targeted delivery to a host
WO2021245611A1 (en) 2020-06-05 2021-12-09 Glaxosmithkline Biologicals Sa Modified betacoronavirus spike proteins
EP4171629A1 (en) * 2020-06-29 2023-05-03 GlaxoSmithKline Biologicals S.A. Adjuvants
EP4196148A1 (en) 2020-08-17 2023-06-21 Universität Basel Lfa-1 signalling mediator for use in cancer therapy
US20240269270A1 (en) 2020-08-24 2024-08-15 Sanofi Pasteur Inc. Covid-19 vaccines with tocopherol-containing squalene emulsion adjuvants
US11225508B1 (en) 2020-09-23 2022-01-18 The University Of North Carolina At Chapel Hill Mouse-adapted SARS-CoV-2 viruses and methods of use thereof
CN113999315B (zh) 2020-10-23 2025-11-14 江苏省疾病预防控制中心(江苏省公共卫生研究院) 融合蛋白及其应用
IL302362A (en) 2020-10-27 2023-06-01 Pfizer ESCHERICHIA COLI preparations and their methods
US12138302B2 (en) 2020-10-27 2024-11-12 Pfizer Inc. Escherichia coli compositions and methods thereof
CA3200602A1 (en) 2020-11-04 2022-05-12 Pfizer Inc. Immunogenic compositions for use in pneumococcal vaccines
CA3200968A1 (en) 2020-11-10 2022-05-19 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
US12357681B2 (en) 2020-12-23 2025-07-15 Pfizer Inc. E. coli FimH mutants and uses thereof
WO2022147373A1 (en) 2020-12-31 2022-07-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins
US20220226465A1 (en) 2021-01-18 2022-07-21 ConserV Bioscience Coronavirus Immunogenic Compositions, Methods and Uses Thereof
EP4032547A1 (en) 2021-01-20 2022-07-27 GlaxoSmithKline Biologicals S.A. Hsv1 fce derived fragements for the treatment of hsv
WO2022178196A1 (en) 2021-02-19 2022-08-25 Sanofi Pasteur Inc. Meningococcal b recombinant vaccine
EP4294433A1 (en) 2021-02-22 2023-12-27 GlaxoSmithKline Biologicals SA Immunogenic composition, use and methods
EP4313137A1 (en) 2021-03-26 2024-02-07 GlaxoSmithKline Biologicals SA Immunogenic compositions
EP4346893A2 (en) 2021-05-28 2024-04-10 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
PE20240090A1 (es) 2021-05-28 2024-01-16 Pfizer Composiciones inmunogenas que comprenden antigenos de sacarido capsular conjugados y sus usos
MX2023015327A (es) 2021-06-28 2024-01-23 Glaxosmithkline Biologicals Sa Antigenos de la influenza novedosos.
WO2023020992A1 (en) 2021-08-16 2023-02-23 Glaxosmithkline Biologicals Sa Novel methods
WO2023020994A1 (en) 2021-08-16 2023-02-23 Glaxosmithkline Biologicals Sa Novel methods
WO2023020993A1 (en) 2021-08-16 2023-02-23 Glaxosmithkline Biologicals Sa Novel methods
WO2023061993A1 (en) 2021-10-13 2023-04-20 Glaxosmithkline Biologicals Sa Polypeptides
EP4433080A1 (en) 2021-11-18 2024-09-25 Matrivax, Inc. Immunogenic fusion protein compositions and methods of use thereof
CA3247998A1 (en) 2022-01-13 2023-07-20 Pfizer Inc. Immunogenic compositions based on conjugated capsular saccharidic antigens and their uses
US20250163484A1 (en) 2022-02-25 2025-05-22 Pfizer Inc. Methods for Incorporating Azido Groups in Bacterial Capsular Polysaccharides
CN114984201B (zh) * 2022-04-24 2025-10-17 国药中生生物技术研究院有限公司 类天然脂滴纳米乳佐剂及其制备方法
AU2023268745A1 (en) 2022-05-11 2024-11-07 Pfizer Inc. Process for producing of vaccine formulations with preservatives
WO2024110827A1 (en) 2022-11-21 2024-05-30 Pfizer Inc. Methods for preparing conjugated capsular saccharide antigens and uses thereof
KR20250107930A (ko) 2022-11-22 2025-07-14 화이자 인코포레이티드 접합된 피막 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도
CN120513083A (zh) 2022-12-01 2025-08-19 辉瑞大药厂 肺炎链球菌缀合物疫苗制剂
EP4637812A1 (en) 2022-12-19 2025-10-29 GlaxoSmithKline Biologicals S.A. Hepatitis b compositions
GB202219228D0 (en) 2022-12-20 2023-02-01 Glaxosmithkline Biologicals Sa Novel influenza antigens
EP4661911A1 (en) 2023-02-10 2025-12-17 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
TW202502375A (zh) 2023-03-02 2025-01-16 法商賽諾菲公司 用於治療披衣菌之組合物
WO2024201324A2 (en) 2023-03-30 2024-10-03 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
KR20250169621A (ko) 2023-04-14 2025-12-03 화이자 인코포레이티드 접합된 피막 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도
WO2024224266A1 (en) 2023-04-24 2024-10-31 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
CN121285384A (zh) 2023-05-05 2026-01-06 赛诺菲巴斯德有限公司 用于在痤疮的治疗中使用的组合物
WO2024241172A2 (en) 2023-05-19 2024-11-28 Glaxosmithkline Biologicals Sa Methods for eliciting an immune response to respiratory syncycial virus and streptococcus pneumoniae infection
WO2025133971A1 (en) 2023-12-23 2025-06-26 Pfizer Inc. Improved methods for producing bacterial capsular saccharide glycoconjugates
WO2025186705A2 (en) 2024-03-06 2025-09-12 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
WO2025191415A1 (en) 2024-03-11 2025-09-18 Pfizer Inc. Immunogenic compositions comprising conjugated escherichia coli saccharides and uses thereof
WO2025219904A1 (en) 2024-04-19 2025-10-23 Pfizer Inc. Improved methods for producing glycoconjugates by reductive amination in aprotic solvent
CN119925590A (zh) * 2025-04-08 2025-05-06 北京华诺泰生物医药科技有限公司 一种mpl复合佐剂及其制备方法和应用

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4606918A (en) * 1983-08-22 1986-08-19 Syntex (U.S.A.) Inc. Polyoxypropylene-polyoxyethylene block polymer based adjuvants
US5554372A (en) * 1986-09-22 1996-09-10 Emory University Methods and vaccines comprising surface-active copolymers
CA1331443C (en) * 1987-05-29 1994-08-16 Charlotte A. Kensil Saponin adjuvant
US5057540A (en) * 1987-05-29 1991-10-15 Cambridge Biotech Corporation Saponin adjuvant
EP0315153B1 (en) * 1987-11-03 1994-05-11 Syntex (U.S.A.) Inc. Vaccine adjuvant
US4912094B1 (en) * 1988-06-29 1994-02-15 Ribi Immunochem Research Inc. Modified lipopolysaccharides and process of preparation
ES2068989T3 (es) * 1989-02-04 1995-05-01 Akzo Nobel Nv Tocoles como adyuvante en vacunas.
HU212924B (en) * 1989-05-25 1996-12-30 Chiron Corp Adjuvant formulation comprising a submicron oil droplet emulsion
NZ238731A (en) * 1990-06-27 1996-02-27 Univ Emory Vaccine adjuvant compositions comprising ethyleneoxy-propyleneoxy-ethyleneoxy block copolymer or a non-toxic lipopolysaccharide
DK0489153T3 (da) * 1990-06-29 2000-01-24 Chiron Corp Vaccinepræparater indeholdende liposomer
US5709879A (en) * 1990-06-29 1998-01-20 Chiron Corporation Vaccine compositions containing liposomes
GB9106048D0 (en) * 1991-03-21 1991-05-08 Smithkline Beecham Biolog Vaccines
AU654970B2 (en) * 1990-09-28 1994-12-01 Smithkline Beecham Biologicals (Sa) Derivatives of gp160 and vaccines based on gp160 or a derivative thereof, containing an adjuvant
GB9105992D0 (en) * 1991-03-21 1991-05-08 Smithkline Beecham Biolog Vaccine
PH30906A (en) 1991-07-25 1997-12-23 Idec Pharma Corp Induction of cytotoxic t-lymphocyte responses.
US6620414B2 (en) 1992-03-27 2003-09-16 Smithkline Beecham Biologicals (S.A.) Hepatitis vaccines containing 3-0-deacylated monophoshoryl lipid A
NZ253137A (en) * 1992-06-25 1996-08-27 Smithkline Beecham Biolog Vaccine comprising antigen and/or antigenic composition, qs21 (quillaja saponaria molina extract) and 3 de-o-acylated monophosphoryl lipid a.
US5776468A (en) * 1993-03-23 1998-07-07 Smithkline Beecham Biologicals (S.A.) Vaccine compositions containing 3-0 deacylated monophosphoryl lipid A
EP0705109B2 (en) * 1993-05-25 2004-01-02 American Cyanamid Company Adjuvants for vaccines against respiratory syncytial virus
GB9326253D0 (en) * 1993-12-23 1994-02-23 Smithkline Beecham Biolog Vaccines
EP1009382B1 (en) 1997-09-05 2003-06-18 GlaxoSmithKline Biologicals S.A. Oil in water emulsions containing saponins
GB9718901D0 (en) 1997-09-05 1997-11-12 Smithkline Beecham Biolog Vaccine

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