CN1086142A - 疫苗 - Google Patents
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Abstract
本发明提供了包含3De-O-酰化的单磷酰类脂
A和QS21的疫苗组合物。该疫苗组合物是CTL和
γIFN应答的有效诱导物。
Description
本发明涉及新的疫苗制剂,其制备方法和其在医药上的应用。具体而言,本发明涉及包含QS21和3-De-O-酰化的单磷酰类脂A(3D-MPL)的疫苗,其中QS21为从Quillaja Saponaria Molina的茎皮得到的经高压液相色谱(Hplc)纯化的无毒成分。
3De-O-酰化的单磷酰类脂A可参见GB2,220,211(Ribi)。从化学上说,它是一种具有4、5或6酰化链的3-脱酰的单磷酰类酯A的混合物,是由Ribi Immunochem Montana制备的。
QS21是一种由南美树种 Ouillaja Saponaria molina的茎皮得到的皂苷经高压液相色谱(HpLe)纯化的无毒成分。其制备方法(以QA21)公开在US5,057,540中。
本发明是以下述惊人发现为基础的,即包含QS21和3D-MPL的组合体的制剂对于某种给定的抗原能协同增强免疫应答。
例如,疟疾抗原RTS,S佐以3D-MPL和QS21的疫苗制剂能有效地协同诱导脾脏中CS蛋白特异的细胞毒素的T淋巴细胞(CTL)的应答。
RTS是一种杂种蛋白,它包含有几乎所有的P.falciparum的环子孢子(CS)蛋白的C-末端部分,经乙肝表面抗原的preS2部分的四个氨基酸连接至乙肝病毒的表面(S)抗原上。其整体结构公开于审查中的国际专利申请PCT/EP92/02591中,以WO93/10152公开,优先权为UK专利申请号9124390.7。当以酵母表达时,RTS以脂蛋白颗粒产生,当其与来自HBV的S抗原一起表达时,产生一种称之为RTS,S的混合颗粒。
能够诱导强烈的溶细胞的T淋巴细胞应答的观测结果意义重大,因为在某些典型动物中这些应答已表现出可诱导对疾病的预防。
本发明人表明,两种佐剂QS21和3D-MPL与重组体颗粒抗原RTS,S的组合体能强有力地诱导脾脏中的CS蛋白特异性CTL.QS21自身也能增强诱导CTL,而3D-MPL则无此作用。可以说这种组合是以一种协同性的方式而起作用,这是因为,其效果大于每种佐剂单独的效果之和。这两种佐剂对CTL诱导的协同作用是一个惊人的发现,它有使用重组体分子作为用于诱导CTL介导的免疫的疫苗的重要结论。
当靶抗原在胞内合成时(如在病毒、胞内细菌的感染中,或在肿瘤中),易于发现CTL的诱导,这是因为由抗原的蛋白水解性分解产生的肽能够进入适宜的处理途径,从而导致与细胞膜上Ⅰ类分子有关的表现。但是,预形成的可溶性抗原通常不会到达该处理和表现途径,也不会诱出Ⅰ类约束的CTL。因而,传统的非活体疫苗在诱出抗体和T辅助应答时通常不能诱导CTL介导的免疫作用。两种佐剂QS21和3D-MPL的组合能够克服基于重组体蛋白的疫苗的这种严重的局限,且能诱导宽范围的免疫应答。
对CS蛋白的CTL特异性已表示出在小鼠模型体系中预防疟疾的功能(Romero等,Nature 341∶323(1989))。对人体进行实验时,使用辐照过的P.falciparum的子孢子使志愿者免疫,表明其可防止随后的疟疾进攻,因而显示出对CS表位特异性的CTL的诱导作用(Malik等Proc.Natl.Acad.Sci.USA.88∶3300(1991))。
由于根据免疫应答的产生和性能,使用辐照的子孢子将是不切实际的,因而诱导对于以重组体分子给药的抗原特异的CTL的能力与疟疾疫苗的开发是有关的。
除了疟疾疫苗,诱导CTL应答的能力还将有益于疫苗抵抗单纯疱疹病毒、细胞肥大病毒、人体免疫缺乏病毒,以及一般地病原体处于胞内生命期的所有病例。
同样,对于已知的肿瘤抗原特异的CTL也能通过一种重组体肿瘤抗原和两种佐剂的组合体进行诱导。这将有益于开发抗癌疫苗。
在一些体系中,3D-MPL和QS21的组合能协同增强干扰素γ的生成。本发明人通过利用称之为gD2t的单纯疱疹抗原表明了3D-MPL和QS21的协同作用潜力。gD2t是一种得自HSV-2的可溶性截断的糖蛋白D,并且可以按Berman等,Science 222 524-527所述的方法在CHO细胞中产生。
IFN-γ分泌与抗胞内病原体的保护性应答有关,所述病原体包括寄生物,细菌和病毒。由INF-γ活化巨噬细胞增强了微生物的胞内杀伤并增加了Fc受体的表达。直接的细胞溶解作用也可能发生,特别是与淋巴毒素(另一种THl细胞的产物)协同作用下发生。IFN-γ不仅是一种诱导物而且是NK细胞的一种产物,NK细胞为主要的先天保护效应物。或者通过IFN-γ或者通过其它机理实现的THI型应答优先有助于IgG2a免疫球蛋白同种型。
糖蛋白D位于病毒被膜上,也能在感染的细胞的细胞质上发现(Eisenberg R.J.等J.Of Virol 1980 35 428-435)。它含有393种包括一种信号肽的氨基酸,其分子量大约为60KD。在所有的HSV被膜糖蛋白中,这可能是最好的特征(Cohen等 J.Virology 60 157-166)。在体内公知它在病毒向细胞膜的附着中起中心作用。进而,糖蛋白D还表明能诱出体内中和抗体(Eing等 J.Med Virology 127∶59-65)。然而,潜伏的HSV2病毒仍然能被再活化并诱导疾病复发,尽管在患者的血清中存在高的中和抗体值。因而很明显,单独诱导中和抗体的能力并不足以适宜地控制疾病。
为了防止疾病复发,任何一种疫苗均需要不仅激发中和抗体,而且要激发通过T细胞特别是细胞毒性T细胞介导的细胞免疫。
在这种情况下,gD2l是308种氨基酸的HSV2糖蛋白D,所述氨基酸包括1至306天然存在的糖蛋白以及在截断蛋白的C末端处的天冬酰胺和谷氨酰胺。这种形式的蛋白包括信号肽,该肽被分成一种成熟的283氨基酸蛋白,在中国大田鼠(Chinese Hamster)的卵巢细胞中这种蛋白的生成在Genentech的EP-B-139417中有述。
从哺乳动物细胞中分泌出的成熟的截断糖蛋白D(rgD2t)或等价的蛋白是在本发明的疫苗制剂中优选使用的。
本发明的制剂能非常有效地诱导天竹鼠的生殖器疱疹模型中的保护免疫。即使采用非常低的抗原剂量(如低至5μg rgD2t),该制剂也能防止天竺鼠的原发感染且能促进特异性中和抗体应答。本发明人采用本发明的制剂已经表明了小鼠中效应物细胞介导的THI型应答。
相应地,本发明提供一种包含有一种抗原及3脱酰单磷酰类酯A和QS21的疫苗或药物制剂。该种制剂可适用于宽范围的单价或多价疫苗。
疫苗制剂最好包含一种抗原或抗原组合物,这种抗原或抗原组合物能够激发对人体或动物病原体的免疫应答,所述抗原或抗原组合物得自于:HIV-1(如gp120或gp160)、任一种猫免疫缺乏病毒、人或动物疱疹病毒如gD或其衍生物或Immediate Early蛋白如由HSV1或HSV2得到的IGP27,细胞肥大病毒(特别是人的)如(gB或其衍生物)、Varicella Zoster Virus(水痘带状疱疹病毒)(如gPⅠ、Ⅱ或Ⅲ),或者得自于:肝类病毒如乙肝病毒如乙型肝炎表面抗原或其衍生物,肝类A病毒、肝炎C病毒和肝炎E病毒,或者得自于其它病毒病原体,如呼吸合胞体病毒、人类乳头状瘤病毒或流感病毒,或者得自于细菌性病原体如Salmonella(沙门氏菌)、Neisseria(奈瑟菌属)、Borrelia(疏螺旋体属)(如OspA或OspB或其衍生物)或Chlamydia(衣原体属)或Bordetella(博氏杆菌属)如P.69,PT和FHA,或者得自于寄生物如疟原虫或Toxoplasma(弓浆虫属)。
制剂还可以包含一种抗肿瘤抗原并用于免疫疗法治疗癌症。
制剂也可以用于与疱疹性轻颗粒一起使用,这些颗粒在国际专利申请PCT/GB92/00824和PCT/GB92/00179中有述。
乙型肝炎表面抗原衍生物在本领域中是公知的,它们包括在EP-A-414374;EP-A-0304578和EP198474中所述的PreS1,PreS2S抗原。
本发明的另一方面是提供了一种如下所述用于药物的疫苗。
QS21与3D-MPL的比值通常在1∶10~10∶1的数量级,优选1∶5~5∶1,更经常的是1∶1。为了最适宜的协同作用优选的范围是2.5∶1~1∶1 3DMPL∶QS21。对于人体给药,典型地在疫苗中每一个剂量中含QS21和3DMPL1μg~100μg,优选10μg-50μg。通常疫苗无需任何特殊的载体,它们能在水或其它药物可接受的缓冲液中配制。在有些情况下,本发明的疫苗最好还包含有明矾,或者是存在于水包油乳液中或其它适宜的载体中,如脂质体、微球体或包囊的抗原颗粒。
疫苗制剂通常描述在下述文献中:New Trends and Developments in Vaccines,由Voller等编辑,University Park Press, Baltimore, Maryland,U.S.A.1978。在脂质体内的包囊也有述,如Fullerton的US4,235,877。蛋白与大分子的结合也有述,如Likhite的US4,372,945和Armor等的US4,474,757。
在每一疫苗剂量中蛋白的量应使其能诱导免疫保护应答但不会在典型的疫苗中造成显著且有害的副作用。这样的用量根据具体所采用的免疫原和它是如何存在的而改变。一般说来,最好每一剂量包含1-1000μg的蛋白,优选2-100μg,最优选4-40μg。对于特定的疫苗来说,其最适宜的用量可通过标准研究方法进行确定,该方法包括对主体观察其适宜的免疫应答。在开始接种后,主体可以接受一次或几次适当间隔的加强免疫接种。
本发明的制剂可用于预防和治疗。
相应地,本发明的另一个方面是提供一种治疗方法,包括对患者施用有效量的本发明的疫苗。
实施例
1.0 对诱导干扰素γ分泌的3D MPL和QS21之间的协同作用
为了测定3D MPL和QS21为佐剂的含rgD2t的制剂诱导效应物细胞介导的免疫应答的能力,对几组Balb/c小鼠进行接种,按下述过程对其排液淋巴结细胞的IFN-γ分泌作用进行测试。
1.1 rgD2t制剂
该实验对三种佐剂的制剂进行比较:
ⅰ)在3D-MPL中的rgD2t
ⅱ)在QS21中的rgD2t
ⅲ)在3D-MPL/QS21中rgD2t
这些制剂制备过程如下:由CHO细胞产生rgD2t且相应于成熟的HSV-2gD的1-283氨基酸,按照Berman(Supra)的方法和EP0139417产生。
*rgD2t/3D-MPL
在搅拌,室温下将5μg rgD2l/剂量培养1小时,然后与3D-MPL悬浮液(25μg/剂量)混合。用氯化钠溶液(5M,PH6.5±0.5)和注射用水调节体积至70μl/剂量得到最后的浓度为0.15M NaCl。PH保持在6.5±0.5。
*rgD2l/QS21
在搅拌,室温下将5μg rgD2l/剂量培养1小时。用氯化钠溶液(5M,PH6.5±0.5)和注射用水调节其体积至70μl。然后加入QS21(10μg/剂量)。保持PH值为6.5±0.5,氯化钠的最后浓度为0.15M。
*rgD2l/3D-MPL/QS21
在搅拌和室温下使5μg rgD2t培养1小时。然后加入3D-MPL(25μg/剂量)的水悬浮液。通过添加QS21(10μg/剂量)的水溶液使最后的体积为70μl,并保持PH值为6.5±0.5,氯化钠浓度为0.15M。
1.2免疫接种
用35μl/爪垫的制剂注射于小鼠的后爪垫中。因此,这样每个小鼠接受了70μl。第零天和第14天进行免疫接种,在第21天将小鼠杀死。
1.3干扰素γ测定
在体外使用10、1、0.1、1、0μg/ml的rgD2l来刺激经免疫的小鼠的腘淋巴结细胞。在园底96孔微量滴定(microtiter)极中作用2×105应答细胞和2×105辐照(3000rad)过的同源的首次用来用实验的脾细胞备好一式三份的培养物(200μl体积)。培养介质是含10%胎儿腓血清的RPMI1640。采集并汇集每一种复试验用的100μl培养介质的等分试样以作IFN-γ测定。培养物在72小时时分析测定。对于所有测定,均包括使用5μg/ml的ConA(Boehringer Mannheim)对照组。各组均呈阳性。
使用Holland Biotechnology(Gibco分部)生产的商用ELISA测定仪测定IFN-γ的分泌。对由一式三份的试样容器得到的100μl汇集的上层清液进行测试。
对所有三种制剂组(见表)观察其以50Pg/μl为实验基准IFN-γ的分泌作用。此外,测得QS21和3D-MPL间的协同效应。虽然每种佐剂自身诱导细胞能分泌IFN-γ对rgD2t作出应答,但它们的组合诱导的应答则比单独每一个应答之和的两倍还多。
1.4结果
IFN-γ以pg/ml表示。
该表清楚地表明了组合的疫苗以协同方式诱导IFN-γ的分泌。
2.0 3D-MPL和QS21对CTLs诱导的协同作用
为了测试在基于3D MPL和QS21的佐剂制剂中的RTS,S颗粒诱导CTLs的能力,对几组B10、BR小鼠进行免疫接种,并在体外刺激它们的脾脏细胞,并对以CS蛋白表示的L细胞的细胞毒性实验进行测试。
2.1RTS,S颗粒的制剂
以三种不同的组成来配制RTS,S颗粒:
1.含QS21(10μg)和3D-MPL(25μg)的RTS,S颗粒(10μg);
2.含QS21(10μg)的RTS,S颗粒(10μg);
3.含3DK-MPL(25μg)的RTS,S颗粒(10μg);
制剂按下述过程制备:
RTS,S/3D MPL
在室温搅拌下培养10μg的RTS,S颗粒/剂量1小时,然后使其与3D MPL水悬浮液(25μg/剂量)混合。用注射用水和氯化钠溶液(5N,PH6.5±0.5)调节体积至70μl/剂量,NaCl的最后浓度为0.15M(PH保持在6.5±0.5)。
RTS,S/QS21
在室温搅拌下培养10μg的RTS,S颗粒/剂量1小时。用注射用水和氯化钠溶液(5N,PH6.5±0.5)调节体积,并用QS21的水溶液(10μg/剂量)使最后的体积为70μl/剂量。PH保持在6.5±0.5,氯化钠的最后浓度为0.15M。
RTS,S/3D MPL/QS21
在室温搅拌下培养10μg的RTS,S颗粒/剂量1小时,然后使其与3D MPL(水悬浮液(25μg/剂量)混合。然后用注射用水和氯化钠溶液(5N PH6.5±0.5)调节其体积。最好的体积通过添加QS21的水溶液(10μg/剂量)来完成。PH值保持6.5±0.5,氯化钠的最后浓度为0.15M。
2.2用RTS,S颗粒对小鼠进行免疫接种
从IFFA CREDO(法国)购买4-6周的B10.BR(H-2K)种雌性小鼠。3个为一组对其进行免疫接种,即在每个后肢内爪垫内注射35μl的抗原制剂。两周后,用第二份相同剂量的抗原注射使小鼠加强接种。
2.3对于抗CS CTL进行体外刺激
被加强后两周,采集脾脏细胞,并用经P.falciparum环子孢子蛋白基因(7G8克隆)转染的同源的成纤维细胞进行体外刺激。这些CS转染子细胞在Kumar,S.等(1988)的文章中有述,Nature 334∶258-260。
在本领域普通技术人员公知的条件下,以补充有10%的热失活的胎儿腓血清的常用的添加剂的RPMI1640介质中确立培养物。
在105CS转染子/ml存在下,以106细胞/ml的浓度对应答细胞进行培养。为了防止CS转染子细胞的再育,用2×104rad的剂量对其进行辐照。在第3天和第6天通过替换1/2的培养介质培育培养物,在第七天测试其细胞溶解活性。
2.4对于抗CS CTL的细胞毒性实验
对应答细胞培养物进行采集、洗涤,并在200μl介质中在V型底96孔板中使其与常数为2000的靶细胞以100∶1~0.3∶1的比例进行混合。
靶细胞是同源的成纤维细胞,它已用51Cr进行标记。
使用两种不同类型的靶细胞:
1.L细胞
2.CS转染的L细胞
它们在下述文献中有述:Kumar,S等(1988),Nature 334∶258-260。
被化验物在37℃下进行培养6小时。测定经靶细胞的溶胞而释放进入上层清液的放射性量。
以%特异性溶胞来表示细胞溶解活性:结果:
用QS21和3D-MPL作佐剂的RTS,S(制剂#1)对B10.BR小鼠的免疫接种在脾中诱导了对于RTS,S的环子孢子组分特异的高含量的CTL。用QS21作佐剂的RTS,S颗粒(制剂#2)的免疫接种也能诱导脾中的CTL,但仅仅是制剂#1所给出的含量的约1/30。用3D-MPL作佐剂的RTS,S(制剂#3)则不能诱导CTL。
由于用于本实验的靶细胞并不表示MHCⅡ级分子,效应物细胞可被假定为CD8+,Ⅰ级限制的CTL。
3.其它制剂
乙型肝炎表面抗原,明矾3D-MPL和QS21。
乙型肝炎表面抗原(HBsAg)的制备已有许多论述,如可参见Harford等,Develop Biol Standard 54 P 125(1983),Gregg等,Biotechnology 5 p479(1987),EP-A-0226846和EP-A-299108,它们均被在此引用作为参考。
3D-MPL由Ribi Immunochem得到,QS21由Cambridge Biotech得到,氢氧化铝由Superfos(Alhydrogel)得到。
制备多种不同的制剂用以研究对小鼠的细胞介导的免疫性及对猕猴进行研究。
3.1在磷酸盐缓冲溶液(PH6.8)中制备制剂1,
每60μl剂量的制剂包含:
20μg HBsAg
30μg Al(OH)3
30μg 3D-MPL
10μg QS21
10mM PO4 3-
0.15M NaCl
制剂按下述过程制备,在室温及温和的振荡下使20μg HBsAg剂量与Al(OH)3培养1小时。随后加入3D-MPL和水悬浮液,通过添加QS21、磷酸盐缓冲液和氯化钠完成制剂制备,并在室温下培养1小时。最后的制剂的PH值在6.5-7.0之间,并将其用于小鼠的爪垫研究。
3.2在磷酸盐缓冲溶液(PH6.8)中制备制剂2,每200μl剂量的制剂包含:
1μg HBsAg
100μg Al(OH)3
50μg 3D-MPL
20μg QS21
10mM PO4 3-
0.15M NaCl
制剂按下述过程制备。在室温及温和的振荡下使用HBsAg与Al(OH)3一起培养1小时。通过添加Al(OH)3、3D-MPL的水悬浮液及QS21,用磷酸盐缓冲液和氯化钠溶液完成制剂的制备,并再培养30分钟。制剂的PH值保持在6.5-7.0之间,它用于小鼠的体液免疫性研究。
3.3用类似的方式在磷酸盐缓冲液(PH6.5-7.0)中制备制剂3,每1ml剂量中包含:
10μg HBsAg
500μg Al(OH)3
50μg 3D-MPL
10μg QS21
制剂被用于猴的研究。
4结论
两种佐剂QS21和3D-MPL与重组体颗粒性抗原RTS,S的组合能有效地诱导脾脏中CS蛋白特异的CTL。QS21自己增强了CTL的诱导,而3D-MPL则不能诱导。这种组合能以协同的方式起作用,由于其作用大于每种佐剂单独效用之和。两种佐剂对CTL诱导的协同性是一个令人惊奇的实验结果,该结果表明了QS21和3D-MPL对T细胞的诱导具有协同作用,所述T细胞能够分泌IFN-γ以应答对用可溶性重组体蛋白gD2t的刺激。该发现对于使用重组体分子用于诱导CTL介导的免疫的疫苗具有重要意义。这是因为两种佐剂QS21和3D-MPL的组合能够克服基于重组体蛋白的疫苗的严重的局限性,并较之现有的疫苗能在更宽范围内诱导免疫应答。
小鼠细胞介导的免疫原性数据表明,基于QS21的rgD2t制剂诱导了显著的协同性THI型T细胞应答(IFN-γ分泌)。
这种THI型T细胞已表明与诱导小鼠延迟型过敏性应答有关。我们自己的预防HSV疾病的数据表明,中和抗体值和抗原特异性DTH应答的伴随诱导对于抵抗单纯疱疹疾病提供最好的防护。
总之,这些数据向我们表明,rgD2t的QS21制剂可以有效地诱导一种保护性应答以抵抗HSV疾病。所提供的数据还表明了3D单磷酰类酯A(3D Monophosphoryl Lipid A)和QS21对于诱导IFN-γ分泌抗原特异性T细胞具有意外的协同作用。这种协同性可以表现为增强诱导保护性应答以抵抗HSV疾病的能力,而且这些制剂的确可有效地防护抵抗天竺鼠的疾病。
Claims (12)
1、一种疫苗组合物,它包含一种抗原和/或抗原组合物、QS21的3De-O-酰化的单磷酰类脂A(3D-MPL)。
2、一种按权利要求1的疫苗,其中QS21与3D-MPL的比值为1∶10-10∶1。
3、一种权利要求1或2所要求保护的疫苗组合物,能够在哺乳动物中对抗原或抗原组合物引起细胞溶解的T细胞应答。
4、一种按权利要求1-3任一项所要求保护的疫苗组合物,能够刺激干扰素γ生成。
5、一种按权利要求1-4任一项所要求保护的疫苗组合物,其中QS21与3D-MPL的比值为1∶1~1∶2.5。
6、一种按以上权利要求的疫苗组合物,包含一种抗原或抗原组合物,它们得自于下述中的任一种:人体免疫缺乏病毒、猫免疫缺乏病毒、单纯疱疹病毒1型、单纯疱疹病毒2型、人体细胞肥大病毒、肝炎A、B、C或E、呼吸全胞体病毒、人体乳头状瘤病毒、流感病毒、沙门氏菌、奈瑟菌属、疏螺旋体属、衣原体属、博代杆菌属、疟原虫属或弓浆虫属。
7、一种按权利要求1-5中任一项所要求保护的疫苗,其中抗原为一种肿瘤抗原。
8、权利要求1-5任一项所限定的组合物的用途,用于制造一种用于预防治疗病毒、细菌或寄生虫感染的疫苗。
9、权利要求1-5任一项所限定的组合物的用途,用于制造一种用于免疫疗法治疗病毒、细菌、寄生虫感染或癌症的疫苗。
10、一种治疗患有或可能被一种病原感染的哺乳动物的方法,该方法包括施用安全且有效量的权利要求1-5任一项的组合物。
11、一种治疗患有癌症的哺乳动物的方法,该方法包括施用安全且有效量的权利要求1-5任一项的组合物。
12、一种制备权利要求1-5的疫苗组合物的方法,该方法包括使QS21和3D-MPL与一种抗原或抗原组合物混合。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100374151C (zh) * | 1997-12-02 | 2008-03-12 | 神经实验室有限公司 | 产生免疫的药物组合物及其在制备预防和治疗致淀粉样病的药物中的用途 |
CN103405764A (zh) * | 2005-12-13 | 2013-11-27 | 葛兰素史密丝克莱恩生物有限公司 | 包含皂苷佐剂的疫苗组合物 |
Families Citing this family (458)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9105992D0 (en) * | 1991-03-21 | 1991-05-08 | Smithkline Beecham Biolog | Vaccine |
UA40597C2 (uk) * | 1992-06-25 | 2001-08-15 | Смітклайн Бічем Байолоджікалс С.А. | Вакцинна композиція,спосіб лікування ссавців, що страждають або сприйнятливі до інфекції, спосіб лікування ссавців, що страждають на рак, спосіб одержання вакцинної композиції, композиція ад'ювантів |
WO1994019013A1 (en) * | 1993-02-19 | 1994-09-01 | Smithkline Beecham Corporation | Influenza vaccine compositions containing 3-o-deacylated monophosphoryl lipid a |
US5773011A (en) * | 1993-09-27 | 1998-06-30 | Gerbu Biotechnik Gmbh | Method of preparing a synergistic immunological adjuvant formulation |
US6083513A (en) * | 1993-11-16 | 2000-07-04 | Gerbu Biotechnik Gmbh | Method for increasing the yield of antibodies in the techniques of immunology |
GB9326253D0 (en) * | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
AUPM446594A0 (en) * | 1994-03-16 | 1994-04-14 | Csl Limited | Cytotoxic t-cell epitopes identified within epstein-barr virus |
GB9506863D0 (en) * | 1995-04-03 | 1995-05-24 | Smithkline Beecham Biolog | Vaccines |
UA56132C2 (uk) * | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
US6846489B1 (en) * | 1995-04-25 | 2005-01-25 | Smithkline Beecham Biologicals S.A. | Vaccines containing a saponin and a sterol |
US20010053365A1 (en) * | 1995-04-25 | 2001-12-20 | Smithkline Beecham Biologicals S.A. | Vaccines |
GB9513261D0 (en) * | 1995-06-29 | 1995-09-06 | Smithkline Beecham Biolog | Vaccines |
ES2283012T3 (es) | 1996-01-04 | 2007-10-16 | Novartis Vaccines And Diagnostics, Inc. | Bacterioferritina de helicobacter pylori. |
US7112331B2 (en) | 1996-02-09 | 2006-09-26 | Smithkline Beecham Biologicals, S.A. | Vaccines against varicella zoster virus gene 63 product |
GB9616351D0 (en) * | 1996-08-02 | 1996-09-11 | Smithkline Beecham Biolog | Vaccine composition |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
GB9706957D0 (en) * | 1997-04-05 | 1997-05-21 | Smithkline Beecham Plc | Formulation |
US6080725A (en) * | 1997-05-20 | 2000-06-27 | Galenica Pharmaceuticals, Inc. | Immunostimulating and vaccine compositions employing saponin analog adjuvants and uses thereof |
US5977081A (en) * | 1997-05-20 | 1999-11-02 | Galenica Pharmaceuticals, Inc. | Triterpene saponin analogs having adjuvant and immunostimulatory activity |
GB9712347D0 (en) * | 1997-06-14 | 1997-08-13 | Smithkline Beecham Biolog | Vaccine |
US7459524B1 (en) * | 1997-10-02 | 2008-12-02 | Emergent Product Development Gaithersburg Inc. | Chlamydia protein, sequence and uses thereof |
GB9724531D0 (en) | 1997-11-19 | 1998-01-21 | Smithkline Biolog | Novel compounds |
US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
BR9907691B1 (pt) | 1998-02-05 | 2011-05-31 | derivado de antìgeno e antìgeno da famìlia mage associado a tumor, seqüência de ácido nucléico, codificando os mesmos, seus usos na preparação de vacina, processo para produção de vacina e vacina. | |
US20020147143A1 (en) | 1998-03-18 | 2002-10-10 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
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 |
KR20060118630A (ko) * | 1998-04-29 | 2006-11-23 | 와이어쓰 홀딩스 코포레이션 | 나이제리아 고노리아 또는 나이제리아 메닌지티디스에 대한재조합 필린을 함유한 백신 |
US6306404B1 (en) | 1998-07-14 | 2001-10-23 | American Cyanamid Company | Adjuvant and vaccine compositions containing monophosphoryl lipid A |
EP2272859B1 (en) | 1998-08-07 | 2014-10-22 | University of Washington | Immunological herpes simplex virus antigens and methods for use thereof |
US6262029B1 (en) | 1998-08-14 | 2001-07-17 | Galenica Pharmaceuticals, Inc. | Chemically modified saponins and the use thereof as adjuvants |
US6692752B1 (en) | 1999-09-08 | 2004-02-17 | Smithkline Beecham Biologicals S.A. | Methods of treating human females susceptible to HSV infection |
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 |
KR100629028B1 (ko) * | 1998-10-16 | 2006-09-26 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 애쥬번트 시스템 및 백신 |
GB9826886D0 (en) * | 1998-12-07 | 1999-01-27 | Smithkline Beecham Biolog | Novel compounds |
EP2374889A3 (en) | 1998-12-08 | 2012-02-22 | GlaxoSmithKline Biologicals SA | Novel compounds |
US20020061848A1 (en) * | 2000-07-20 | 2002-05-23 | Ajay Bhatia | Compounds and methods for treatment and diagnosis of chlamydial infection |
KR100829407B1 (ko) | 1998-12-08 | 2008-05-15 | 코릭사 코포레이션 | 클라미디아 감염을 치료 및 진단하기 위한 조성물 및 이를 포함하는 약제학적 조성물 및 진단 키트 |
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 |
ATE451461T1 (de) | 1999-03-12 | 2009-12-15 | Glaxosmithkline Biolog Sa | Antigene polypeptide aus neisseria meningitidis, dafür kodierende polynukleotide und entsprechende schützende antikörper |
AR022963A1 (es) | 1999-03-19 | 2002-09-04 | Smithkline Beecham Biolog | Vacuna |
GB9909077D0 (en) * | 1999-04-20 | 1999-06-16 | Smithkline Beecham Biolog | Novel compositions |
IL145731A0 (en) | 1999-04-02 | 2002-07-25 | Corixa Corp | A polypetide containing an immunogenic portion of a breast tumor protein and pharmaceutical compositions containing the same |
WO2000062800A2 (en) | 1999-04-19 | 2000-10-26 | Smithkline Beecham Biologicals Sa | Adjuvant composition comprising saponin and an immunostimulatory oligonucleotide |
US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
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 |
GB9919468D0 (en) | 1999-08-17 | 1999-10-20 | Smithkline Beecham Biolog | Vaccine |
CA2721011A1 (en) | 1999-10-22 | 2001-05-03 | Aventis Pasteur Limited | Modified gp100 and uses thereof |
GB0000891D0 (en) * | 2000-01-14 | 2000-03-08 | Allergy Therapeutics Ltd | Formulation |
US20030158134A1 (en) * | 2000-01-31 | 2003-08-21 | Gerald Voss | Vaccine for the prophylactic or therapeutic immunization against hiv |
DE60143425D1 (de) | 2000-02-23 | 2010-12-23 | Smithkline Beecham Biolog | Neue verbindungen |
US20040002068A1 (en) | 2000-03-01 | 2004-01-01 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
US6919187B2 (en) * | 2000-04-21 | 2005-07-19 | Corixa Corporation | Compounds and methods for treatment and diagnosis of chlamydial infection |
EP2192128A3 (en) | 2000-04-21 | 2010-09-22 | Corixa Corporation | Compounds and methods for treatment and diagnosis of chlamydial infection |
CA2408328C (en) | 2000-05-10 | 2012-04-17 | Aventis Pasteur Limited | Immunogenic polypeptides encoded by mage minigenes and uses thereof |
JP5139618B2 (ja) | 2000-06-20 | 2013-02-06 | コリクサ コーポレイション | Mycobacteriumtuberculosisの融合タンパク質 |
JP2004513615A (ja) | 2000-06-28 | 2004-05-13 | コリクサ コーポレイション | 肺癌の治療および診断のための組成物および方法 |
GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
HU227893B1 (en) | 2000-06-29 | 2012-05-29 | Glaxosmithkline Biolog Sa | Vaccine compositions |
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 |
US20050019340A1 (en) | 2000-10-18 | 2005-01-27 | Nathalie Garcon | Vaccines |
EP1201250A1 (en) * | 2000-10-25 | 2002-05-02 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Immunogenic compositions comprising liver stage malarial antigens |
EP2277895B1 (en) | 2000-10-27 | 2013-08-14 | Novartis Vaccines and Diagnostics S.r.l. | Nucleic acids and proteins from streptococcus groups A & B |
US6892140B1 (en) | 2000-11-27 | 2005-05-10 | Enteron, Inc. | Immunogenic cancer peptides and uses thereof |
US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
EP2336368A1 (en) | 2000-12-07 | 2011-06-22 | Novartis Vaccines and Diagnostics, Inc. | Endogenous retroviruses up-regulated in prostate cancer |
GB0103171D0 (en) | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
JP5208347B2 (ja) | 2001-02-23 | 2013-06-12 | 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 | 新規なワクチン |
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 |
US20020193295A1 (en) * | 2001-05-04 | 2002-12-19 | Emanuel Calenoff | Immunogenic peptides and uses thereof |
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 |
MY134424A (en) | 2001-05-30 | 2007-12-31 | Saechsisches Serumwerk | Stable influenza virus preparations with low or no amount of thiomersal |
GB0115176D0 (en) | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
US8481043B2 (en) | 2001-06-22 | 2013-07-09 | Cpex Pharmaceuticals, Inc. | Nasal immunization |
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 |
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 |
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. |
ES2405790T3 (es) | 2001-12-17 | 2013-06-03 | Corixa Corporation | Composiciones y métodos para la terapia y el diagnóstico de enfermedad inflamatoria del intestino |
US7030094B2 (en) * | 2002-02-04 | 2006-04-18 | Corixa Corporation | Immunostimulant compositions comprising an aminoalkyl glucosaminide phosphate and QS-21 |
CA2476626A1 (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 |
ES2368907T3 (es) | 2002-04-19 | 2011-11-23 | The Governing Council Of The University Of Toronto | Procedimientos y composiciones inmunológicas para el tratamiento de la enfermedad de alzheimer. |
ATE545651T1 (de) | 2002-06-13 | 2012-03-15 | Novartis Vaccines & Diagnostic | Vektoren zur expression von hml-2-polypeptiden |
EP2011510B1 (en) | 2002-07-18 | 2011-01-12 | University of Washington | Pharmaceutical compositions comprising immunologically active herpes simplex virus (HSV) protein fragments |
US20060034854A1 (en) | 2002-08-02 | 2006-02-16 | Berthet Francois-Xavier J | Vaccine composition comprising transferrin binding protein and hsf from gram negative bacteria |
GB0220194D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
DE60335477D1 (de) | 2002-10-11 | 2011-02-03 | Novartis Vaccines & Diagnostic | Polypeptidimpstoffe zum breiten schutz gegen hypervirulente meningokokken-linien |
NZ539509A (en) | 2002-10-23 | 2008-05-30 | Glaxosmithkline Biolog Sa | Priming vaccine comprising a polynucleotide encoding at least one first malarial antigen and a boosting vaccine comprising at least one polypeptide comprising at least one second malarial antigen having at least one epitope in common with the first malarial antigen of the priming vaccine |
ATE466875T1 (de) | 2002-11-15 | 2010-05-15 | Novartis Vaccines & Diagnostic | Unerwartete oberflächenproteine in neisseria meningitidis |
GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
EP1998177A3 (en) | 2003-01-06 | 2009-02-18 | 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 |
GB0308198D0 (en) | 2003-04-09 | 2003-05-14 | Chiron Srl | ADP-ribosylating bacterial toxin |
TWI374893B (en) | 2003-05-30 | 2012-10-21 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
CA2528007C (en) | 2003-06-02 | 2012-03-27 | Chiron Corporation | Immunogenic compositions based on microparticles comprising adsorbed toxoid and a polysaccharide-containing antigen |
US20060035242A1 (en) | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
SG147465A1 (en) | 2003-09-02 | 2008-11-28 | Glaxosmithkline Biolog Sa | Vaccine |
US8574596B2 (en) | 2003-10-02 | 2013-11-05 | Glaxosmithkline Biologicals, S.A. | Pertussis antigens and use thereof in vaccination |
CA2885040C (en) | 2003-10-02 | 2018-10-30 | Novartis Vaccines And Diagnostics S.R.L. | Liquid vaccines for multiple meningococcal serogroups |
GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
GB0323965D0 (en) * | 2003-10-13 | 2003-11-19 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
CA2551560A1 (en) | 2003-12-23 | 2005-07-14 | Arbor Vita Corporation | Antibodies for oncogenic strains of hpv and methods of their use |
EP1730182B1 (en) | 2004-02-05 | 2015-04-29 | The Ohio State University Research Foundation | Chimeric vegf peptides |
CA2559371C (en) | 2004-03-09 | 2014-07-08 | Chiron Corporation | Influenza virus vaccines |
PL1740217T3 (pl) | 2004-04-30 | 2012-03-30 | Novartis Ag | Szczepienie koniugatem meningokokowym |
GB0500787D0 (en) | 2005-01-14 | 2005-02-23 | Chiron Srl | Integration of meningococcal conjugate vaccination |
GB0409745D0 (en) | 2004-04-30 | 2004-06-09 | Chiron Srl | Compositions including unconjugated carrier proteins |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
ES2647491T3 (es) | 2004-05-21 | 2017-12-21 | Novartis Vaccines And Diagnostics, Inc. | Vectores del alfavirus para las vacunas del virus de la gripe |
GB0411411D0 (en) * | 2004-05-21 | 2004-06-23 | Glaxosmithkline Biolog Sa | Vaccines |
AU2005285513B2 (en) | 2004-05-25 | 2011-02-24 | Oregon Health And Science University | SIV and HIV vaccination using RhCMV- and HCMV-based vaccine vectors |
DE602005025342D1 (de) | 2004-05-28 | 2011-01-27 | Glaxosmithkline Biolog Sa | Impfstoffzusammensetzungen mit virosomen und einem saponin-adjuvans |
EP1784211A4 (en) | 2004-07-29 | 2010-06-30 | Novartis Vaccines & Diagnostic | IMMUNOGENIC COMPOSITIONS FOR GRAMPOSITIVE BACTERIA SUCH AS STREPTOCOCCUS AGALACTIAE |
GB0417494D0 (en) | 2004-08-05 | 2004-09-08 | Glaxosmithkline Biolog Sa | Vaccine |
GB0420634D0 (en) * | 2004-09-16 | 2004-10-20 | Glaxosmithkline Biolog Sa | Vaccines |
KR101508563B1 (ko) | 2004-09-22 | 2015-04-07 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 스태필로코쿠스에 대한 예방접종에 사용하기 위한 면역원성 조성물 |
DK3312272T3 (da) | 2004-10-08 | 2019-12-02 | Us Gov Health & Human Services | Modulering af replikationstilpasning ved brug a mindre optrædende synonyme kodoner |
GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
JP2008523815A (ja) | 2004-12-15 | 2008-07-10 | エラン ファーマ インターナショナル リミテッド | 認知の改善における使用のためのヒト化アミロイドβ抗体 |
CA2590974C (en) | 2005-01-27 | 2017-10-03 | Children's Hospital & Research Center At Oakland | Gna1870-based vesicle vaccines for broad spectrum protection against diseases caused by neisseria meningitidis |
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 |
CN101203529A (zh) | 2005-02-18 | 2008-06-18 | 诺华疫苗和诊断公司 | 来自脑膜炎/脓毒症相关性大肠杆菌的蛋白质和核酸 |
ES2595363T3 (es) | 2005-02-18 | 2016-12-29 | J. Craig Venter Institute, Inc. | Sepsis asociada a las proteínas y los ácidos nucleicos de meningitis / Escherichia coli |
GB0504436D0 (en) | 2005-03-03 | 2005-04-06 | Glaxosmithkline Biolog Sa | Vaccine |
SG158145A1 (en) | 2005-03-31 | 2010-01-29 | Glaxosmithkline Biolog Sa | Vaccines against chlamydial infection |
EP2457926B1 (en) | 2005-04-29 | 2014-09-24 | GlaxoSmithKline Biologicals S.A. | Novel method for preventing or treating M. tuberculosis infection |
JP5222134B2 (ja) | 2005-06-15 | 2013-06-26 | ザ オハイオ ステート ユニバーシティー リサーチ ファウンデーション | Her−2ペプチド |
GB0513421D0 (en) * | 2005-06-30 | 2005-08-03 | Glaxosmithkline Biolog Sa | Vaccines |
EP1910410B1 (en) | 2005-07-01 | 2011-10-26 | Forsyth Dental Infirmary for Children | Tuberculosis antigen detection assays and vaccines |
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 |
NZ568210A (en) * | 2005-11-04 | 2012-12-21 | Novartis Vaccines & Diagnostic | Emulsions with free aqueous-phase surfactant as adjuvants for split influenza vaccines |
AU2006310163B2 (en) | 2005-11-04 | 2011-09-15 | Seqirus UK Limited | Influenza vaccine with reduced amount of oil-in-water emulsion as adjuvant |
EP2377551A3 (en) | 2005-11-04 | 2013-04-24 | Novartis Vaccines and Diagnostics S.r.l. | Adjuvanted influenza vaccines including cytokine-inducing agents |
PT2368572T (pt) | 2005-11-04 | 2020-06-16 | Seqirus Uk Ltd | Vacinas com adjuvante dotadas de antigénios não-virião preparados a partir de vírus da gripe cultivado em cultura celular |
US7527801B2 (en) | 2005-11-22 | 2009-05-05 | Novartis Vaccines And Diagnostics, Inc. | Norovirus and Sapovirus antigens |
GB0524066D0 (en) | 2005-11-25 | 2006-01-04 | Chiron Srl | 741 ii |
GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
CA2816182C (en) | 2005-12-22 | 2018-02-20 | Glaxosmithkline Biologicals S.A. | Pneumococcal polysaccharide conjugate vaccine |
JP2009522011A (ja) | 2005-12-30 | 2009-06-11 | Tti・エルビュー株式会社 | 活性物質を生体界面に送達するイオントフォレーシスシステム、装置及び方法 |
US9259463B2 (en) | 2006-01-16 | 2016-02-16 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Chlamydia vaccine |
ZA200805602B (en) | 2006-01-17 | 2009-12-30 | Arne Forsgren | A novel surface exposed haemophilus influenzae protein (protein E; pE) |
ES2619160T7 (es) | 2006-01-27 | 2020-07-29 | Seqirus Uk Ltd | Vacunas contra la gripe que contienen hemaglutinina y proteínas de la matriz |
ES2388556T3 (es) | 2006-03-23 | 2012-10-16 | Novartis Ag | Compuestos inmunopotenciadores |
ES2536426T3 (es) | 2006-03-23 | 2015-05-25 | Novartis Ag | Compuestos de imidazoquinoxalina como inmunomoduladores |
JP2009534303A (ja) | 2006-03-24 | 2009-09-24 | 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 ゲーエムベーハー アンド カンパニー カーゲー | 冷蔵しないインフルエンザワクチンの保存 |
US20100021503A1 (en) | 2006-03-30 | 2010-01-28 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
US20070243212A1 (en) | 2006-03-30 | 2007-10-18 | Embrex, Inc. | Methods and compositions for vaccination of poultry |
US10138279B2 (en) | 2006-04-13 | 2018-11-27 | Regents Of The University Of Michigan | Compositions and methods for Bacillus anthracis vaccination |
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 |
US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
TW200806315A (en) | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
EP2390359A1 (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 differential expression of the ICOS gene |
DK2054431T3 (da) | 2006-06-09 | 2012-01-02 | Novartis Ag | Konformere af bakterielle adhæsiner |
CA2654709A1 (en) | 2006-06-12 | 2007-12-21 | Nathalie Devos | Neisseria meningitidis lipooligosaccharide vaccine |
AU2007276217B2 (en) | 2006-07-18 | 2013-08-29 | Glaxosmithkline Biologicals S.A. | Vaccines for malaria |
GB0614460D0 (en) | 2006-07-20 | 2006-08-30 | Novartis Ag | Vaccines |
GB2453475B (en) | 2006-07-25 | 2011-01-19 | Secr Defence | Live vaccine strain |
EP2064230A2 (en) | 2006-08-16 | 2009-06-03 | Novartis AG | Immunogens from uropathogenic escherichia coli |
EP2465532A1 (en) * | 2006-08-31 | 2012-06-20 | Baylor Research Institute | JC virus vaccine |
EP2066344B2 (en) | 2006-09-07 | 2016-06-29 | GlaxoSmithKline Biologicals S.A. | Inactivated Poliovirus combination vaccine |
CA3016948A1 (en) | 2006-09-11 | 2008-03-20 | Seqirus UK Limited | Making influenza virus vaccines without using eggs |
US20090181078A1 (en) | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
SI2068918T1 (sl) | 2006-09-26 | 2012-09-28 | Infectious Disease Res Inst | Si - ep sestavek za cepljenje, ki vsebuje sintetiäśna pomagala |
EA200900784A1 (ru) | 2006-12-06 | 2009-12-30 | Новартис Аг | Вакцины, включающие антиген из четырех штаммов вируса гриппа |
HUE031411T2 (en) | 2007-03-02 | 2017-07-28 | Glaxosmithkline Biologicals Sa | New Methods and Preparations |
MX2009010800A (es) | 2007-04-04 | 2010-01-29 | Infectious Disease Res Inst Id | Composiciones inmunogenicas que comprenden polipeptidos de mycobacterium tuberculosis y fusiones de los mismos. |
US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
JP2010525035A (ja) | 2007-05-02 | 2010-07-22 | 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 |
KR101579947B1 (ko) | 2007-06-26 | 2015-12-28 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 스트렙토코쿠스 뉴모니애 캡슐 다당류 컨쥬게이트를 포함하는 백신 |
PL2185191T3 (pl) | 2007-06-27 | 2013-02-28 | Novartis Ag | Szczepionki przeciwko grypie o małej zawartości dodatków |
GB0713880D0 (en) | 2007-07-17 | 2007-08-29 | Novartis Ag | Conjugate purification |
JP5889529B2 (ja) | 2007-07-27 | 2016-03-22 | ヤンセン・サイエンシズ・アイルランド・ユーシー | アミロイド原性疾患の処置 |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
CN101795709B (zh) * | 2007-08-02 | 2013-07-17 | 彼昂德瓦克斯医药有限公司 | 多亚基多表位流感疫苗 |
WO2009020553A2 (en) | 2007-08-03 | 2009-02-12 | President And Fellows Of Harvard College | Chlamydia antigens |
KR20100068390A (ko) | 2007-08-13 | 2010-06-23 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 백신 |
WO2009034473A2 (en) | 2007-09-12 | 2009-03-19 | Novartis Ag | Gas57 mutant antigens and gas57 antibodies |
US9050280B2 (en) | 2007-09-17 | 2015-06-09 | Mdxhealth Sa | Methylation detection of MGMT |
EP2045263A1 (en) | 2007-10-02 | 2009-04-08 | Universite Libre De Bruxelles | Identification and molecular characterisation of salivary metalloproteases expressed in the tick salivary glands |
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 |
AU2008331800A1 (en) | 2007-12-03 | 2009-06-11 | President And Fellows Of Harvard College | Chlamydia antigens |
AU2008352942B2 (en) | 2007-12-19 | 2013-09-12 | 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 |
RU2498994C2 (ru) | 2007-12-21 | 2013-11-20 | Новартис Аг | Мутантные формы стрептолизина о |
EP4219566A3 (en) * | 2007-12-24 | 2023-09-06 | ID Biomedical Corporation of Quebec | Recombinant rsv antigens |
ES2532946T3 (es) | 2008-02-21 | 2015-04-06 | Novartis Ag | Polipéptidos PUfH meningocócicos |
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 |
WO2009127666A2 (en) * | 2008-04-15 | 2009-10-22 | Glaxosmithkline Biologicals S.A. | Method and compositions |
US9527906B2 (en) | 2008-04-18 | 2016-12-27 | The General Hospital Corporation | Immunotherapies employing self-assembling vaccines |
US8877208B2 (en) | 2008-05-23 | 2014-11-04 | The Regents Of The University Of Michigan | Multivalent nanoemulsion vaccines |
MX2011000668A (es) * | 2008-07-18 | 2011-07-29 | Id Biomedical Corp Quebec | Antigenos quimericos polipeptidicos del virus sincitial respiratorio. |
MX2011000981A (es) | 2008-07-25 | 2011-03-02 | Glaxosmithkline Biolog Sa | Composiciones y metodos novedosos. |
PL2315834T3 (pl) | 2008-07-25 | 2018-12-31 | Glaxosmithkline Biologicals S.A. | Białko rv2386c związane z gruźlicą, jego kompozycje i zastosowania |
CA2733356C (en) | 2008-08-01 | 2016-06-07 | Gamma Vaccines Pty Limited | Influenza vaccines |
GB0815872D0 (en) | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
US20100092526A1 (en) | 2008-09-26 | 2010-04-15 | Nanobio Corporation | 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 |
WO2010057197A1 (en) | 2008-11-17 | 2010-05-20 | The Regents Of The University Of Michigan | Cancer vaccine compositions and methods of using the same |
EP2356225A1 (en) | 2008-12-03 | 2011-08-17 | Protea Vaccine Technologies Ltd. | GLUTAMYL tRNA SYNTHETASE (GtS) FRAGMENTS |
ES2622562T3 (es) | 2008-12-09 | 2017-07-06 | Pfizer Vaccines Llc | Vacuna de péptido CH3 de IgE |
CN103897045A (zh) | 2009-01-12 | 2014-07-02 | 诺华股份有限公司 | 抗革兰氏阳性细菌疫苗中的Cna_B结构域 |
GB0901423D0 (en) | 2009-01-29 | 2009-03-11 | Secr Defence | Treatment |
GB0901411D0 (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 |
US8460674B2 (en) | 2009-02-07 | 2013-06-11 | University Of Washington | HSV-1 epitopes and methods for using same |
EP2396032B1 (en) | 2009-02-10 | 2016-09-28 | Seqirus UK Limited | Influenza vaccines with reduced amounts of squalene |
EP3549602A1 (en) | 2009-03-06 | 2019-10-09 | GlaxoSmithKline Biologicals S.A. | Chlamydia antigens |
CN102575284A (zh) | 2009-03-17 | 2012-07-11 | MDx健康公司 | 改进的基因表达检测 |
US9044447B2 (en) | 2009-04-03 | 2015-06-02 | University Of Washington | Antigenic peptide of HSV-2 and methods for using same |
GB0906234D0 (en) | 2009-04-14 | 2009-05-20 | Secr Defence | Vaccine |
EP2510947B1 (en) | 2009-04-14 | 2016-02-10 | GlaxoSmithKline Biologicals SA | Compositions for immunising against Staphylococcus aureus |
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 |
EP2437753B1 (en) | 2009-06-05 | 2016-08-31 | Infectious Disease Research Institute | Synthetic glucopyranosyl lipid adjuvants and vaccine compositions containing them |
EP2442826B1 (en) | 2009-06-15 | 2015-07-08 | National University of Singapore | Influenza vaccine, composition, and methods of use |
EP2442827B1 (en) | 2009-06-16 | 2016-01-06 | The Regents of the University of Michigan | Nanoemulsion vaccines |
MX2012000036A (es) | 2009-06-24 | 2012-02-28 | Glaxosmithkline Biolog Sa | Vacuna. |
AU2010264688A1 (en) | 2009-06-24 | 2012-01-19 | Glaxosmithkline Biologicals S.A. | Recombinant RSV antigens |
JP2012532600A (ja) | 2009-07-07 | 2012-12-20 | ノバルティス アーゲー | 保存された大腸菌免疫原 |
CN105214080A (zh) | 2009-07-15 | 2016-01-06 | 诺华股份有限公司 | Rsv f蛋白组合物和其制作方法 |
PL2464658T3 (pl) | 2009-07-16 | 2015-03-31 | Novartis Ag | Immunogeny z Escherichia coli o zniesionej toksyczności |
JP2013500326A (ja) | 2009-07-30 | 2013-01-07 | ファイザー バクシーンズ エルエルシー | 抗原性タウペプチドおよびその使用 |
GB0913681D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
CN107715118A (zh) * | 2009-08-26 | 2018-02-23 | 西莱克塔生物科技公司 | 诱导t细胞辅助的组合物 |
CN104650241A (zh) | 2009-08-27 | 2015-05-27 | 诺华股份有限公司 | 包括脑膜炎球菌fHBP序列的杂交多肽 |
PE20161551A1 (es) | 2009-09-03 | 2017-01-18 | Pfizer Vaccines Llc | Vacuna de pcsk9 |
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 |
CA2779798C (en) | 2009-09-30 | 2019-03-19 | Novartis Ag | Conjugation of staphylococcus aureus type 5 and type 8 capsular polysaccharides |
US20130022639A1 (en) | 2009-09-30 | 2013-01-24 | Novartis Ag | Expression of meningococcal fhbp polypeptides |
GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
US20130022633A1 (en) | 2009-10-27 | 2013-01-24 | University Of Florence | MENINGOCOCCAL fHBP POLYPEPTIDES |
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 |
CA2785585A1 (en) | 2009-12-22 | 2011-06-30 | Celldex Therapeutics, Inc. | Vaccine compositions |
JP5781542B2 (ja) | 2009-12-30 | 2015-09-24 | ノバルティス アーゲー | E.coliキャリアタンパク質に結合体化した多糖免疫原 |
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 |
CA2793959C (en) | 2010-03-25 | 2019-06-04 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
JP2013523617A (ja) | 2010-03-26 | 2013-06-17 | 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 | Hivワクチン |
US9827300B2 (en) | 2010-03-30 | 2017-11-28 | Children's Hospital & Research Center Oakland | Factor H binding proteins (FHBP) with altered properties and methods of use thereof |
GB201005625D0 (en) | 2010-04-01 | 2010-05-19 | Novartis Ag | Immunogenic proteins and compositions |
BR112012025364A2 (pt) | 2010-04-07 | 2015-09-22 | Novartis Ag | método para geração de partícula semelhante a vírus de parvovírus b19 |
NO2575876T3 (zh) | 2010-05-26 | 2018-05-05 | ||
CN102933267B (zh) | 2010-05-28 | 2015-05-27 | 泰特里斯在线公司 | 交互式混合异步计算机游戏基础结构 |
ES2614807T3 (es) | 2010-06-04 | 2017-06-02 | Wyeth Llc | Formulaciones vacunales |
CA2800774A1 (en) | 2010-06-07 | 2011-12-15 | 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 |
AU2011276328C1 (en) | 2010-07-06 | 2016-01-21 | Novartis Ag | Norovirus derived immunogenic compositions and methods |
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 |
MX354752B (es) | 2010-09-27 | 2018-03-20 | Janssen Vaccines & Prevention Bv | Regimen de vacunacion de sensibilizacion y refuerzo heterologo contra malaria. |
JP2014501225A (ja) | 2010-09-27 | 2014-01-20 | 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 |
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 |
WO2012057904A1 (en) | 2010-10-27 | 2012-05-03 | Infectious Disease Research Institute | Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity |
EP2637687B1 (en) | 2010-11-08 | 2021-01-06 | 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 |
CN103282375B (zh) | 2010-12-02 | 2017-01-11 | 比奥诺尔免疫有限公司 | 肽支架设计 |
CA2860331A1 (en) | 2010-12-24 | 2012-06-28 | Novartis Ag | Compounds |
GB201022007D0 (en) | 2010-12-24 | 2011-02-02 | Imp Innovations Ltd | DNA-sensor |
JP6294076B2 (ja) | 2011-01-06 | 2018-03-14 | ビオノール イミュノ エーエスBionor Immuno As | 多量体ペプチド |
EP2667892B1 (en) | 2011-01-26 | 2019-03-27 | GlaxoSmithKline Biologicals SA | Rsv immunization regimen |
AU2012211043B2 (en) | 2011-01-27 | 2017-04-06 | 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 |
US9321813B2 (en) | 2011-03-29 | 2016-04-26 | Uab Research Foundation | Methods and compositions for cytomegalovirus IL-10 protein |
GB201106357D0 (en) | 2011-04-14 | 2011-06-01 | Pessi Antonello | Composition and uses thereof |
EA027236B1 (ru) | 2011-04-08 | 2017-07-31 | Иммьюн Дизайн Корп. | Иммуногенные композиции и способы применения таких композиций для индукции гуморального и клеточного иммунного ответа |
TW201302779A (zh) | 2011-04-13 | 2013-01-16 | Glaxosmithkline Biolog Sa | 融合蛋白質及組合疫苗 |
PT3275892T (pt) | 2011-05-13 | 2020-04-08 | Glaxosmithkline Biologicals Sa | Antigénios f de rsv de pré-fusão |
EP2717909B1 (en) | 2011-06-04 | 2017-12-06 | Rochester General Hospital Research Institute | Compositions and methods related to p6 of haemophilus influenzae |
CA2832109C (en) | 2011-06-10 | 2021-07-06 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
WO2012177595A1 (en) | 2011-06-21 | 2012-12-27 | Oncofactor Corporation | Compositions and methods for the therapy and diagnosis of cancer |
ES2687129T3 (es) | 2011-07-25 | 2018-10-23 | Glaxosmithkline Biologicals Sa | Composiciones y métodos para evaluar la inmunogenicidad funcional de vacunas contra parvovirus |
CA2843274A1 (en) | 2011-07-29 | 2013-02-07 | Selecta Biosciences, Inc. | Synthetic nanocarriers that generate humoral and cytotoxic t lymphocyte (ctl) immune responses |
GB201113570D0 (en) | 2011-08-05 | 2011-09-21 | Glaxosmithkline Biolog Sa | Vaccine |
GB201114919D0 (en) | 2011-08-30 | 2011-10-12 | Glaxosmithkline Biolog Sa | Method |
GB201114923D0 (en) | 2011-08-30 | 2011-10-12 | Novartis Ag | Immunogenic proteins and compositions |
WO2013038185A1 (en) | 2011-09-12 | 2013-03-21 | Jonathan Norden Weber | Methods and compositions for raising an immune response to hiv |
EP2568289A3 (en) | 2011-09-12 | 2013-04-03 | International AIDS Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
EP2755683B1 (en) | 2011-09-14 | 2019-04-03 | GlaxoSmithKline Biologicals SA | Methods for making saccharide-protein glycoconjugates |
CN103930436A (zh) | 2011-09-14 | 2014-07-16 | 诺华股份有限公司 | 大肠杆菌疫苗组合 |
CA2848611A1 (en) | 2011-09-16 | 2013-03-21 | Ucb Pharma S.A. | Neutralising antibodies to the major exotoxins tcda and tcdb of clostridium difficile |
US9402894B2 (en) | 2011-10-27 | 2016-08-02 | International Aids Vaccine Initiative | Viral particles derived from an enveloped virus |
US20130122038A1 (en) | 2011-11-14 | 2013-05-16 | The United States Of America As Represented By The Secretary Of The Department | Heterologous prime-boost immunization using measles virus-based vaccines |
BR112014013876A2 (pt) | 2011-12-08 | 2019-09-24 | Novartis Ag | vacina à base de toxina de clostridium difficile |
WO2013108272A2 (en) | 2012-01-20 | 2013-07-25 | International Centre For Genetic Engineering And Biotechnology | Blood stage malaria vaccine |
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 |
EP2817320A1 (en) | 2012-02-24 | 2014-12-31 | Novartis AG | Pilus proteins and compositions |
WO2013134577A2 (en) | 2012-03-08 | 2013-09-12 | Detectogen, Inc. | Leishmaniasis antigen detection assays and vaccines |
ES2702278T3 (es) | 2012-04-01 | 2019-02-28 | Technion Res & Dev Foundation | Péptidos de inductor de metaloproteinasa de matriz extracelular (emmprin) y anticuerpos de unión |
BR112014024612A2 (pt) | 2012-04-02 | 2021-06-08 | Univ North Carolina Chapel Hill | ácido nucleico, polipeptídeo, glicoproteína e quimérica, epítopo de vírus da dengue, partícula semelhante a flavivírus quimérico (vlp), flavivírus quimérico, e métodos in vitro para identificar um anticorpo neutralizante e para identificar uma composição imunogênica contra um vírus da dengue |
US10279026B2 (en) | 2012-04-26 | 2019-05-07 | Glaxosmithkline Biologicals Sa | Antigens and antigen combinations |
RU2727476C2 (ru) | 2012-04-26 | 2020-07-21 | Новартис Аг | Антигены и антигенные композиции |
EP2659906A1 (en) * | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
EP2659908A1 (en) | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
EP2659907A1 (en) * | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
US9169304B2 (en) | 2012-05-01 | 2015-10-27 | Pfenex Inc. | Process for purifying recombinant Plasmodium falciparum circumsporozoite protein |
SG10201603896RA (en) | 2012-05-04 | 2016-07-28 | Pfizer | Prostate-associated antigens and vaccine-based immunotherapy regimens |
MX350274B (es) | 2012-05-16 | 2017-08-31 | Immune Design Corp | Vacunas para hsv-2. |
MX2014014067A (es) | 2012-05-22 | 2015-02-04 | Novartis Ag | Conjugado de serogrupo x de meningococo. |
EP2666785A1 (en) | 2012-05-23 | 2013-11-27 | Affiris AG | Complement component C5a-based vaccine |
CA2874923C (en) | 2012-06-06 | 2021-08-31 | Bionor Immuno As | Peptides derived from viral proteins for use as immunogens and dosage reactants |
ES2631608T3 (es) | 2012-06-27 | 2017-09-01 | International Aids Vaccine Initiative | Variante de la glicoproteína Env del VIH-1 |
JP2015525784A (ja) | 2012-08-03 | 2015-09-07 | インフェクティアス ディジーズ リサーチ インスティチュート | 活動性結核菌感染を治療するための組成物及び方法 |
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 |
AU2013320313B2 (en) | 2012-09-18 | 2018-07-12 | Glaxosmithkline Biologicals Sa | Outer membrane vesicles |
EA201590427A1 (ru) | 2012-10-02 | 2015-09-30 | Глаксосмитклайн Байолоджикалс С.А. | Нелинейные сахаридные конъюгаты |
SG11201500978TA (en) | 2012-10-03 | 2015-07-30 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
ES2854754T3 (es) | 2012-10-24 | 2021-09-22 | Platelet Targeted Therapeutics Llc | Tratamiento dirigido a plaquetas |
DK2925355T3 (en) | 2012-11-30 | 2018-01-15 | Glaxosmithkline Biologicals Sa | PSEUDOMONAS ANTIGENES AND ANTIGEN COMBINATIONS |
WO2014086787A1 (en) | 2012-12-05 | 2014-06-12 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
BR112015024860B1 (pt) | 2013-03-28 | 2023-11-07 | Access To Advanced Health Institute | Polipeptídeo de fusão, polinucleotídeo isolado, composição compreendendo dito polipeptídeo, uso da dita composição para estimular uma resposta imune contra leishmania e método in vitro e kit de diagnóstico para detectar infecção por leishmania em uma amostra biológica |
BR112015025709A2 (pt) | 2013-04-18 | 2017-07-18 | Immune Design Corp | monoterapia com gla para uso em tratamento de câncer |
CA2909586C (en) | 2013-05-15 | 2021-08-31 | 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 |
CN110734500A (zh) | 2013-06-26 | 2020-01-31 | 北卡罗来纳-查佩尔山大学 | 用于登革病毒疫苗的方法与组合物 |
US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
US10208102B2 (en) | 2013-11-01 | 2019-02-19 | University Of Oslo | Albumin variants and uses thereof |
CA2929126C (en) | 2013-11-13 | 2020-01-07 | 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 |
WO2015092710A1 (en) | 2013-12-19 | 2015-06-25 | Glaxosmithkline Biologicals, S.A. | Contralateral co-administration of vaccines |
US9868769B2 (en) | 2014-01-06 | 2018-01-16 | The United States Of America, As Represented By The Secretary Of Agriculture | Mutated Salmonella enteriaca |
CN114887048A (zh) | 2014-01-21 | 2022-08-12 | 辉瑞公司 | 包含缀合荚膜糖抗原的免疫原性组合物及其用途 |
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 |
CA2943190A1 (en) * | 2014-03-25 | 2015-10-01 | The Government Of The United States Of America As Represented By The Secretary Of The Army | Non-toxic adjuvant formulation comprising a monophosphoryl lipid a (mpla)-containing liposome composition and a saponin |
LT3160500T (lt) | 2014-06-25 | 2019-10-25 | Glaxosmithkline Biologicals Sa | Clostridium difficile imunogeninė kompozicija |
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 |
NZ766003A (en) | 2014-07-23 | 2024-01-26 | Children’S Hospital & Res Center At Oakland | Factor h binding protein variants and methods of use thereof |
ES2924988T3 (es) | 2014-10-10 | 2022-10-13 | Univ Michigan Regents | Composiciones con nanoemulsiones para prevenir, inhibir o eliminar una enfermedad alérgica e inflamatoria |
EP3212672A4 (en) | 2014-11-02 | 2018-04-25 | The University of North Carolina at Chapel Hill | Methods and compositions for recombinant dengue viruses for vaccine and diagnostic development |
US20170281744A1 (en) | 2014-12-10 | 2017-10-05 | Glaxosmithkline Biologicals Sa | Method of treatment |
BR112017013891B1 (pt) | 2015-01-15 | 2024-01-30 | Pfizer Inc | Composições imunogênicas para uso em vacinas pneumocócicas |
WO2016134300A1 (en) | 2015-02-20 | 2016-08-25 | Board Of Regents, The University Of Texas System | Methods and compositions for attenuated chlamydia as vaccine and vector |
EP3261667A4 (en) * | 2015-02-26 | 2018-10-24 | TheVax Genetics Vaccine Co., Ltd. | A vaccine composition comprising an immunogenic protein and combination adjuvants for use in eliciting antigen-specific t-cell responses |
CN107530416A (zh) | 2015-03-05 | 2018-01-02 | 西北大学 | 非神经侵染的病毒及其用途 |
US20180071380A1 (en) | 2015-03-20 | 2018-03-15 | The Regents Of The University Of Michigan | Immunogenic compositions for use in vaccination against bordetella |
US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
US9931394B2 (en) | 2015-03-23 | 2018-04-03 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
CN116603058A (zh) | 2015-03-26 | 2023-08-18 | Gpn疫苗有限公司 | 链球菌疫苗 |
BR112017025316A2 (pt) | 2015-05-26 | 2018-07-31 | Ohio State Innovation Foundation | estratégia de vacina baseada em nanopartículas contra o vírus da gripe suína |
AU2016271857B2 (en) | 2015-06-03 | 2020-05-28 | Affiris Ag | IL-23-P19 vaccines |
BR112017028011A2 (pt) | 2015-06-26 | 2018-08-28 | Seqirus Uk Ltd | vacinas de gripe correspondentes antigenicamente |
US20180186896A1 (en) | 2015-07-07 | 2018-07-05 | Affiris Ag | Vaccines for the treatment and prevention of ige mediated diseases |
WO2017013548A1 (en) | 2015-07-21 | 2017-01-26 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
CN108431214B (zh) | 2015-10-05 | 2022-03-01 | 美国政府(由卫生和人类服务部的部长所代表) | 人轮状病毒g9p[6]毒株和作为疫苗的用途 |
GB201518668D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Immunogenic Comosition |
CA3005524C (en) | 2015-11-20 | 2023-10-10 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
BE1024160B9 (fr) | 2015-12-22 | 2017-12-06 | Glaxosmithkline Biologicals Sa | Formulation immunogène |
TWI654302B (zh) | 2016-01-19 | 2019-03-21 | 輝瑞股份有限公司 | 癌症疫苗 |
WO2017137085A1 (en) | 2016-02-11 | 2017-08-17 | Sanofi Pasteur | Meningitidis vaccines comprising subtilinases |
CN109562154A (zh) | 2016-03-10 | 2019-04-02 | 爱普瑞希斯有限公司 | 带有修饰hsp70域的抗原结合融合蛋白 |
KR20180127320A (ko) | 2016-03-14 | 2018-11-28 | 유니버시티에트 이 오슬로 | 변경된 FcRn 결합을 갖는 조작된 면역글로불린 |
WO2017158421A1 (en) | 2016-03-14 | 2017-09-21 | University Of Oslo | Anti-viral engineered immunoglobulins |
KR102392974B1 (ko) | 2016-05-16 | 2022-05-02 | 인펙셔스 디지즈 리서치 인스티튜트 (아이디알아이) | Tlr 작용제를 함유하는 제제 및 사용 방법 |
WO2017201390A1 (en) | 2016-05-19 | 2017-11-23 | The Regents Of The University Of Michigan | Novel adjuvant compositions |
EP3458088A2 (en) | 2016-05-21 | 2019-03-27 | Infectious Disease Research Institute | Compositions and methods for treating secondary tuberculosis and nontuberculous mycobacterium infections |
MX2021010105A (es) | 2016-06-01 | 2022-06-16 | Infectious Disease Res Inst | Particulas de nanoalumbre que contienen un agente de dimensionamiento. |
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 |
MX2019003035A (es) | 2016-09-16 | 2019-09-13 | Infectious Disease Res Inst | Vacunas que comprenden polipeptidos de mycobacterium leprae para la prevencion, el tratamiento y el diagnostico de la lepra. |
WO2018060288A1 (en) | 2016-09-29 | 2018-04-05 | Glaxosmithkline Biologicals S.A. | Compositions and methods of treatment of persistent hpv infection |
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 |
GB201621686D0 (en) * | 2016-12-20 | 2017-02-01 | Glaxosmithkline Biologicals Sa | Novel methods for inducing an immune response |
HRP20220573T1 (hr) | 2017-01-20 | 2022-06-10 | Pfizer Inc. | Imunogeni pripravci, namijenjeni upotrebi u pneumokoknim cjepivima |
WO2018178265A1 (en) | 2017-03-31 | 2018-10-04 | Glaxosmithkline Intellectual Property Development Limited | Immunogenic composition, use and method of treatment |
JP2020515587A (ja) | 2017-03-31 | 2020-05-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 免疫原性組成物、使用及び処置方法 |
EP3615005A4 (en) * | 2017-04-28 | 2021-03-10 | The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. | VACCINATION COMPOSITIONS AND METHODS |
EP3641808A1 (en) | 2017-08-14 | 2020-04-29 | GlaxoSmithKline Biologicals S.A. | Methods of boosting immune responses |
US11123415B2 (en) | 2017-08-16 | 2021-09-21 | Ohio State Innovation Foundation | Nanoparticle compositions for Salmonella vaccines |
WO2019048936A1 (en) | 2017-09-07 | 2019-03-14 | University Of Oslo | VACCINE MOLECULES |
EP3678698A1 (en) | 2017-09-07 | 2020-07-15 | University Of Oslo | Vaccine molecules |
US20200276299A1 (en) | 2017-09-08 | 2020-09-03 | Infectious Disease Research Institute | Liposomal formulations comprising saponin and methods of use |
EP3681534A1 (en) | 2017-09-13 | 2020-07-22 | Sanofi Pasteur | Human cytomegalovirus immunogenic composition |
US11566050B2 (en) | 2017-10-18 | 2023-01-31 | The University Of North Carolina At Chapel Hill | Methods and compositions for norovirus vaccines and diagnostics |
GB201721068D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B immunisation regimen and compositions |
GB201721069D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
WO2019173438A1 (en) | 2018-03-06 | 2019-09-12 | Stc. Unm | Compositions and methods for reducing serum triglycerides |
TW201946650A (zh) | 2018-03-12 | 2019-12-16 | 美商詹森藥物公司 | 針對腹內感染之疫苗 |
US11702674B2 (en) | 2018-06-12 | 2023-07-18 | Glaxosmithkline Biologicals Sa | Simian adenovirus vectors comprising the ChAd-157 fiber protein |
BR112021000965A2 (pt) | 2018-08-07 | 2021-04-27 | Glaxosmithkline Biologicals S.A. | processos e vacinas |
JP2021534761A (ja) | 2018-08-23 | 2021-12-16 | 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 | 免疫原性タンパク質および組成物 |
US11260119B2 (en) | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
EP3851120A4 (en) | 2018-09-11 | 2022-04-27 | Shanghai Public Health Clinical Center | IMMUNOGEN FOR BROAD-SPECTRUM INFLUENZA VACCINE, AND APPLICATION THEREOF |
EP3890775A1 (en) | 2018-12-06 | 2021-10-13 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
WO2020121159A1 (en) | 2018-12-12 | 2020-06-18 | Pfizer Inc. | Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof |
EP3897846A1 (en) | 2018-12-21 | 2021-10-27 | 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 |
US20220339281A1 (en) | 2019-03-05 | 2022-10-27 | GalxoSmithKline Biologicals SA | Hepatitis b immunisation regimen and compositions |
PE20212265A1 (es) | 2019-03-18 | 2021-11-30 | Janssen Pharmaceuticals Inc | Bioconjugados de antigenos-polisacaridos de e. coli, metodos de produccion y metodos de utilizacion de los mismos |
SG11202110303XA (en) | 2019-03-18 | 2021-10-28 | Janssen Pharmaceuticals Inc | Methods of producing bioconjugates of e. coli o-antigen polysaccharides, compositions thereof, and methods of use thereof |
JP2022528158A (ja) | 2019-04-10 | 2022-06-08 | ファイザー・インク | コンジュゲート化莢膜糖抗原を含む免疫原性組成物、それを含むキットおよびその使用 |
EP3956666A1 (en) | 2019-04-18 | 2022-02-23 | GlaxoSmithKline Biologicals S.A. | Antigen binding proteins and assays |
BR112021026565A2 (pt) | 2019-08-05 | 2022-05-03 | Glaxosmithkline Biologicals Sa | Composição imunogênica |
EP3777884A1 (en) | 2019-08-15 | 2021-02-17 | GlaxoSmithKline Biologicals S.A. | Immunogenic composition |
EP3799884A1 (en) | 2019-10-01 | 2021-04-07 | GlaxoSmithKline Biologicals S.A. | Immunogenic compositions |
EP4038091A1 (en) | 2019-10-02 | 2022-08-10 | Janssen Vaccines & Prevention B.V. | Staphylococcus peptides and methods of use |
JP2021087420A (ja) | 2019-11-01 | 2021-06-10 | ファイザー・インク | Escherichia coli組成物およびその方法 |
WO2021122551A1 (en) | 2019-12-19 | 2021-06-24 | Glaxosmithkline Biologicals Sa | S. aureus antigens and compositions thereof |
JP2023500749A (ja) | 2020-01-16 | 2023-01-10 | ヤンセン ファーマシューティカルズ,インコーポレーテッド | FimH変異体、その組成物、及びその使用 |
NL2030835B1 (en) | 2020-01-24 | 2022-12-29 | Aim Immunotech Inc | Methods, compositions, and vaccinces for treating a virus infection |
EP4103587A1 (en) | 2020-02-14 | 2022-12-21 | Immunor AS | Corona virus vaccine |
AU2021224078B2 (en) | 2020-02-21 | 2024-01-18 | Pfizer Inc. | Purification of saccharides |
AU2021223184A1 (en) | 2020-02-23 | 2022-08-18 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
WO2022029024A1 (en) | 2020-08-03 | 2022-02-10 | Glaxosmithkline Biologicals Sa | Truncated fusobacterium nucleatum fusobacterium adhesin a (fada) protein and immunogenic compositios thereof |
PE20231385A1 (es) | 2020-09-17 | 2023-09-12 | Janssen Pharmaceuticals Inc | Composiciones de vacunas multivalentes y usos de las mismas |
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 |
WO2022083768A1 (zh) | 2020-10-23 | 2022-04-28 | 江苏省疾病预防控制中心(江苏省公共卫生研究院) | 免疫原性组合物及其应用 |
CA3199610A1 (en) | 2020-10-27 | 2022-05-05 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
IL302413A (en) | 2020-11-04 | 2023-06-01 | Pfizer | Immunogenic preparations for use in pneumococcal vaccines |
US20230405137A1 (en) | 2020-11-10 | 2023-12-21 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US20220202923A1 (en) | 2020-12-23 | 2022-06-30 | 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 |
KR20230125842A (ko) | 2021-01-12 | 2023-08-29 | 얀센 파마슈티칼즈, 인코포레이티드 | FimH 돌연변이체, 이를 포함하는 조성물 및 이의 용도 |
EP4277654A1 (en) | 2021-01-18 | 2023-11-22 | Conserv Bioscience Limited | Coronavirus immunogenic compositions, methods and uses thereof |
US20220265805A1 (en) | 2021-02-19 | 2022-08-25 | Sanofi Pasteur Inc. | Meningococcal b recombinant vaccine |
JP2024510717A (ja) | 2021-02-22 | 2024-03-11 | 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 | 免疫原性組成物、使用及び方法 |
IL307247A (en) | 2021-04-01 | 2023-11-01 | Janssen Pharmaceuticals Inc | Production of E. Coli O18 bioconjugates |
CA3221074A1 (en) | 2021-05-28 | 2022-12-01 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
CA3221075A1 (en) | 2021-05-28 | 2022-12-01 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023092090A1 (en) | 2021-11-18 | 2023-05-25 | Matrivax, Inc. | Immunogenic fusion protein compositions and methods of use thereof |
WO2023135515A1 (en) | 2022-01-13 | 2023-07-20 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023161817A1 (en) | 2022-02-25 | 2023-08-31 | Pfizer Inc. | Methods for incorporating azido groups in bacterial capsular polysaccharides |
WO2023218322A1 (en) | 2022-05-11 | 2023-11-16 | Pfizer Inc. | Process for producing of vaccine formulations with preservatives |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4235877A (en) | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
US4372945A (en) | 1979-11-13 | 1983-02-08 | Likhite Vilas V | Antigen compounds |
IL61904A (en) | 1981-01-13 | 1985-07-31 | Yeda Res & Dev | Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same |
NZ209308A (en) | 1983-08-30 | 1991-08-27 | Genentech Inc | Vaccine against hsv involving a truncated membrane-free derivative of a membrane-bound protein |
FI861417A0 (fi) | 1985-04-15 | 1986-04-01 | Endotronics Inc | Hepatitis b ytantigen framstaelld med rekombinant-dna-teknik, vaccin, diagnostiskt medel och cellinjer samt foerfaranden foer framstaellning daerav. |
US4895800A (en) | 1985-11-26 | 1990-01-23 | Phillips Petroleum Company | Yeast production of hepatitis B surface antigen |
US4877611A (en) * | 1986-04-15 | 1989-10-31 | Ribi Immunochem Research Inc. | Vaccine containing tumor antigens and adjuvants |
US5057540A (en) * | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
EP0304578B1 (en) | 1987-06-22 | 2001-10-24 | Medeva Holdings Bv | Peptide comprising hepatitis B surface antigen |
ES2056799T3 (es) | 1987-07-17 | 1994-10-16 | Rhein Biotech Ges Fur Biotechn | Moleculas de adn codante para las regiones de control fmdh y gen estructural para una proteina que tiene una actividad de fmdh y su uso. |
AU632493B2 (en) * | 1988-05-03 | 1993-01-07 | Lg Electronics Inc. | Microprocessor having external control store |
US4912094B1 (en) * | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
SG48175A1 (en) | 1989-07-25 | 1998-04-17 | Smithkline Beecham Biolog | Novel antigens and method for their preparation |
EP0614465B1 (en) | 1991-11-16 | 1999-03-17 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | HYBRID PROTEIN BETWEEN CS FROM PLASMODIUM AND HBsAG |
UA40597C2 (uk) * | 1992-06-25 | 2001-08-15 | Смітклайн Бічем Байолоджікалс С.А. | Вакцинна композиція,спосіб лікування ссавців, що страждають або сприйнятливі до інфекції, спосіб лікування ссавців, що страждають на рак, спосіб одержання вакцинної композиції, композиція ад'ювантів |
-
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100374151C (zh) * | 1997-12-02 | 2008-03-12 | 神经实验室有限公司 | 产生免疫的药物组合物及其在制备预防和治疗致淀粉样病的药物中的用途 |
CN103405764A (zh) * | 2005-12-13 | 2013-11-27 | 葛兰素史密丝克莱恩生物有限公司 | 包含皂苷佐剂的疫苗组合物 |
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