Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences
    2.
    发明申请
    Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences 失效
    杂种或嵌合多核苷酸,蛋白质和包含乙型肝炎病毒序列的组合物

    公开(公告)号:US20040018208A1

    公开(公告)日:2004-01-29

    申请号:US10388337

    申请日:2003-03-14

    申请人: Institut Pasteur

    摘要: H-2 class I negative, HLA-A2.1 transgeniic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumor-associated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.

    摘要翻译: 使用H-2 I型阴性,HLA-A2.1转基因HHD小鼠进行HLA-A2.1限制性人肿瘤相关CTL表位的免疫原性的比较评估。 在IFA中注射到小鼠中的这些表位肽之间建立了等级关系,其全局与其结合和稳定HLA-A2.1分子的能力相关。 辅助肽的共注射增强了大多数CTL应答。 相比之下,仍然表达自己的I类分子的经典HLA I类转基因小鼠在大多数情况下并不在相同的实验条件下产生H.A.-A2.1限制性CTL应答。 在HHD小鼠中比较了可接受的临床应用的不同单表位免疫策略。 重组的Ty病毒样颗粒或编码与乙型肝炎病毒中膜包膜蛋白融合的表位的DNA得到最好的结果。 使用后一种方法和基于黑素瘤的多表位构建体,可以在单个动物中同时诱导针对五种不同表位的CTL应答。 因此,HHD小鼠为基于肽的癌症免疫治疗的临床前评估提供了通用的动物模型。

    Vaccines expressed in plants
    6.
    发明申请

    公开(公告)号:US20030138456A1

    公开(公告)日:2003-07-24

    申请号:US09918937

    申请日:2001-07-31

    摘要: The anti-viral vaccine of the present invention is produced in transgenic plants and then administered through standard vaccine introduction method or through the consumption of the edible portion of those plants. A DNA sequence encoding for the expression of a surface antigen of a viral pathogen is isolated and ligated to a promoter which can regulate the production of the surface antigen in a transgenic plant. This gene is then transferred to plant cells using a procedure that results in its integration into the plant genome, such as through the use of an Agrobacterium tumenfaciens plasmid vector system. Preferably, the foreign gene is expressed in an portion of the plant that is edible by humans or animals. In a preferred procedure, the vaccine is administered through the consumption of the edible plant as food, preferably in the form of a fruit or vegetable juice which can be taken orally.

    Hepatitis B virus surface antigen mutant and methods of detection thereof
    8.
    发明申请
    Hepatitis B virus surface antigen mutant and methods of detection thereof 有权
    乙型肝炎病毒表面抗原突变体及其检测方法

    公开(公告)号:US20040209248A1

    公开(公告)日:2004-10-21

    申请号:US10847493

    申请日:2004-05-17

    摘要: The subject invention relates to a novel hepatitis B surface antigen mutant and methods of detecting this mutant, and/or antibodies thereto, in patient samples. In particular, the mutant contains a substitution of amino acid threonine for the amino acid alanine at position 123 in the amino acid sequence of the hepatitis B surface antigen (HBsAg) protein.

    摘要翻译: 本发明涉及一种新型乙型肝炎表面抗原突变体和在该患者样品中检测该突变体和/或其抗体的方法。 特别地,突变体含有氨基酸苏氨酸取代乙型肝炎表面抗原(HBsAg)蛋白质的氨基酸序列中123位的氨基酸丙氨酸。

    Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection
    9.
    发明申请
    Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection 有权
    密码子优化的针对人巨细胞病毒感染的基于多核苷酸的疫苗

    公开(公告)号:US20040209241A1

    公开(公告)日:2004-10-21

    申请号:US10738986

    申请日:2003-12-19

    摘要: The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.

    摘要翻译: 本发明涉及基于多核苷酸的巨细胞病毒疫苗。 特别地,本发明是可操作地编码HCMV抗原的质粒,其中用于HCMV抗原的天然存在的编码区已通过密码子优化被修饰以改善人或其他哺乳动物细胞中的翻译。 可用于本发明的HCMV抗原包括但不限于pp65,糖蛋白B(gB),IE1以及这些抗原之一的片段,变体或衍生物。 在某些实施方案中,已经删除了序列,例如pp65中的Arg435-Lys438推定的激酶和gB中的膜锚定和内细胞域。 本发明还涉及在哺乳动物例如人中诱导对HCMV的免疫应答的方法,其包括如上所述递送编码密码子优化的HCMV抗原的质粒。 本发明还涉及包含编码如上所述的密码子优化的HCMV抗原的质粒的药物组合物,并且还包含佐剂,赋形剂或免疫调节剂。

    Method for obtaining antigenic aggregates and the use thereof in formulations
    10.
    发明申请
    Method for obtaining antigenic aggregates and the use thereof in formulations 审中-公开
    获得抗原聚集体的方法及其在制剂中的用途

    公开(公告)号:US20040202676A1

    公开(公告)日:2004-10-14

    申请号:US10433492

    申请日:2004-03-01

    摘要: The present invention is related to the method for obtaining aggregated antigenic structures that are capable of enhancing an immune response to aggregate antigens administered systemically and/or mucosally generating powerful immune response and to the chemical structures resulting from the application of said method, to the formulations obtained from such structures and their use. The method describes the obtention of novel aggregate antigenic structures by using aggregating, delipidating or oxidating agents or compounds enabling the release of lipids from the particles and their heterogeneous aggregation, wherein aggregates with particle sizes of between 30 and 500 nm are subsequently selected by means of a molecular exclusion process. The aggregation state can also be provoket inside the yeast by changing incubation conditions. The resulting structures can be used conveniently adjuvated or in a formulation in which several antigens can be introduced, wherein synergism between said components is found with respect to the immunogenicity of the response obtained. The preparation may also contain stabilizers and preservatives. The resulting antigenic structures can be used in the pharmaceutical industry as preventive or therapeutic vaccine formulation both for human and veterinary use and as part of diagnostic system.

    摘要翻译: 本发明涉及获得聚集的抗原结构的方法,所述聚集的抗原结构能够增强对于全身施用和/或粘膜产生强大的免疫应答的聚集抗原的免疫应答和由所述方法应用所产生的化学结构的制剂 从这样的结构和它们的使用获得。 该方法描述了通过使用聚集,脱脂或氧化剂或能够从颗粒中释放脂质及其不均匀聚集的新型聚集抗原结构的获得,其中随后通过以下步骤选择粒度为30-500nm的聚集体: 分子排除过程。 聚集状态也可以通过改变孵育条件在酵母内进行。 所得到的结构可以方便地用于佐剂或在可以引入几种抗原的制剂中,其中发现所述组分之间的协同作用与获得的反应的免疫原性有关。 该制剂还可含有稳定剂和防腐剂。 所得到的抗原结构可用于制药工业,作为用于人类和兽医用途的预防或治疗疫苗制剂,并且作为诊断系统的一部分。