公开(公告)号：US6066623A

公开(公告)日：2000-05-23

申请号：US155888

申请日：1993-11-23

申请人： Stephen L. Hoffman ,  Richard C. Hedstrom ,  Martha Sedegah

发明人： Stephen L. Hoffman ,  Richard C. Hedstrom ,  Martha Sedegah

IPC分类号： A61K39/00 ,  C07K14/11 ,  C07K14/235 ,  C07K14/445 ,  A61K48/00 ,  C12N5/00 ,  C12N15/00

CPC分类号： C07K14/005 ,  C07K14/235 ,  C07K14/445 ,  A61K2039/53 ,  A61K39/00 ,  C12N2760/16122 ,  Y10S514/895

摘要： A first embodiment is a specific plasmid vector, pDIP/PyCSP.1, into which nucleotides encoding the targets of specific immune responses are inserted. These targets include, but are not limited to proteins and peptides. These plasmid constructs are incorporated in a composition comprising a suitable and acceptable art recognized pharmaceutical reagent that is benign (non-reactive with) to the plasmid construct. The plasmid construct provides protective immune responses to the disease associated with the selected targets. A second embodiment is a construct having, at a minimum, the nucleotide sequences encoding one or more Plasmodium species proteins in a pharmaceutically acceptable vector. a third embodiment is a method of controlling malaria in mammals comprising injecting a polynucleotide delivery vector into a mammal.

摘要翻译： 第一个实施方案是特异性质粒载体pDIP / PyCSP.1，其中插入编码特异性免疫应答靶标的核苷酸。 这些靶标包括但不限于蛋白质和肽。 将这些质粒构建体并入包含与质粒构建体良性（非反应性）的合适且可接受的本领域公认的药物试剂的组合物中。 质粒构建体对与所选靶标相关的疾病提供保护性免疫应答。 第二个实施方案是至少在药学上可接受的载体中具有编码一种或多种疟原虫物质蛋白质的核苷酸序列的构建体。 第三个实施方案是控制哺乳动物疟疾的方法，包括将多核苷酸递送载体注射到哺乳动物中。

公开(公告)号：US5814617A

公开(公告)日：1998-09-29

申请号：US319704

申请日：1994-10-07

申请人： Stephen L. Hoffman ,  Yupin Charoenvit ,  Richard C. Hedstrom ,  Denise L. Doolan

发明人： Stephen L. Hoffman ,  Yupin Charoenvit ,  Richard C. Hedstrom ,  Denise L. Doolan

IPC分类号： A61K39/00 ,  C07K14/445 ,  A61K31/505

CPC分类号： C07K14/445 ,  A61K39/00

摘要： An IgG1 monoclonal antibody, Navy Yoelii Liver Stage 3 (NYLS3) does not recognize sporozoites, but recognizes P. yoelii liver stage parasites within 6 hours of invasion of mouse hepatocytes, and throughout the hepatic and asexual erythrocytic stages of the life cycle. When added to primary cultures of mouse hepatocytes 24 hours after inoculation with P. yoelii sporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood stage parasitemia after sporozoite or blood stage challenge. The protein recognized by this mAb is identified and designated P. yoelii hepatic and erythrocytic stage protein, 17-kDa or PyHEP17. The gene encoding PyHEP17 and a DNA vaccine comprising exons of the DNA that encodes PyHEP17 are disclosed. A DNA vaccine consisting of exon 1 and part of exon 2 of the gene encoding PyHEP17 protects 86% of A/J mice, 33%-43% of B10.BR mice, 17%-29% of BALB/c mice and 14%-20% of B10.Q mice from development of blood-stage parasitemia. A combination of DNA vaccines consisting of a PyHEP17 DNA vaccine and a PyCSP DNA vaccine confers complete protection against development of blood-stage parasitemia in BALB/c mice and 71% protection in A/J and B10.BR mice. This DNA vaccine-induced protection may be additive. Combinations of other malaria antigens are covered. The application discloses the P. falciparum homolog of PyHEP17 and includes the means of identification of the PyHEP17 homologs of the other Plasmodium species which infect humans, specifically P. vivax, P. ovale and P. malariae.

摘要翻译： IgG1单克隆抗体，海军Yoelii肝阶段3（NYLS3）不识别子孢子，但是在侵入小鼠肝细胞的6小时内，以及生命周期的整个肝和无性红细胞阶段中，识别约氏疟原虫肝阶段寄生虫。 当接种约氏疟原虫子鼠24小时后，当所有子孢子侵入肝细胞时，NYLS3消除高达98％的肝阶段寄生虫，当被添加到小鼠肝细胞的原代培养物时。 将静脉注射NYLS3给小鼠延迟发作，并减少子孢子或血液阶段挑战后血液寄生虫血症的密度。 鉴定并鉴定了该mAb所识别的蛋白质，并将其命名为约氏杆菌肝和红细胞期蛋白，17-kDa或PyHEP17。 公开了编码PyHEP17的基因和包含编码PyHEP17的DNA的外显子的DNA疫苗。 由编码PyHEP17基因的外显子1和外显子2组成的DNA疫苗保护86％的A / J小鼠，33％-43％的B10.BR小鼠，17％-29％的BALB / c小鼠和14％ -20％的B10.Q小鼠发展为血液寄生虫血症。 由PyHEP17 DNA疫苗和PyCSP DNA疫苗组成的DNA疫苗的组合可以完全保护BALB / c小鼠中血液寄生虫血症的发展，在A / J和B10.BR小鼠中具有71％的保护作用。 这种DNA疫苗诱导的保护可能是添加剂。 其他疟疾抗原的组合被覆盖。 该申请公开了PyHEP17的恶性疟原虫同系物，并且包括鉴定感染人的其他疟原虫物种的PyHEP17同系物的方法，特别是间日疟原虫，卵白念珠菌和疟原虫。