公开(公告)号：US06749857B1

公开(公告)日：2004-06-15

申请号：US09376463

申请日：1999-08-18

申请人： Iain D. Peters ,  Beth-Ann G. Coller ,  Michael McDonell ,  John M. Ivy ,  Kent Harada

发明人： Iain D. Peters ,  Beth-Ann G. Coller ,  Michael McDonell ,  John M. Ivy ,  Kent Harada

IPC分类号： A01J2100

CPC分类号： C07K14/005 ,  A61K39/00 ,  C07K2319/00 ,  C12N2770/24122 ,  Y02A50/386

摘要： The present invention discloses and claims vaccines containing, as an active ingredient, a secreted recombinantly produced dimeric form of truncated flaviviral envelope protein. The vaccines are capable of eliciting the production of neutralizing antibodies against flaviviruses. The dimeric forms of truncated flaviviral envelope protein are formed 1) by directly linking two tandem copies of 80% E in a head to tail fashion via a flexible tether; 2) via the formation of a leucine zipper domain through the homodimeric association of two leucine zipper helices each fused to the carboxy terminus of an 80% E molecule; or 3) via the formation of a non-covalently associated four-helix bundle domain formed upon association of two helix-turn-helix moieties each attached to the carboxy terminus of an 80% E molecule. All products are expressed as a polyprotein including prM and the modified 80% E products are secreted from Drosophila melanogaster Schneider 2 cells using the human tissue plasminogen activator secretion signal sequence (tPAL). Secreted products are generally more easily purified than those expressed intracellularly, facilitating vaccine production. One embodiment of the present invention is directed to a vaccine for protection of a subject against infection by dengue virus. The vaccine contains, as active ingredient, the dimeric form of truncated envelope protein of a dengue virus serotype. The dimeric truncated E is secreted as a recombinantly produced protein from eucaryotic cells. The vaccine may further contain portions of additional dengue virus serotype dimeric E proteins similarly produced. Another embodiment of the present invention is directed to methods to utilize the dimeric form of truncated dengue envelope protein for diagnosis of infection in individuals at risk for the disease. The diagnostic contains, as active ingredient, the dimeric form of truncated envelope protein of a dengue virus serotype. The dimeric truncated E is secreted as a recombinantly produced protein from eucaryotic cells. The diagnostic may further contain portions of additional dengue virus serotype dimeric E proteins similarly produced.

公开(公告)号：US06432411B1

公开(公告)日：2002-08-13

申请号：US09352387

申请日：1999-07-13

申请人： John Ivy ,  Gary Bignami ,  Michael McDonell ,  David E. Clements ,  Beth-Ann G. Coller

发明人： John Ivy ,  Gary Bignami ,  Michael McDonell ,  David E. Clements ,  Beth-Ann G. Coller

IPC分类号： A61K3912

CPC分类号： A61K39/12 ,  A61K39/39 ,  A61K2039/55505 ,  A61K2039/55566 ,  A61K2039/55577 ,  A61K2039/70 ,  C12N2770/24134 ,  Y02A50/386 ,  Y02A50/39

摘要： A vaccine contains at least one Drosophila cell-secreted, recombinantly-produced form of a truncated Flavivirus envelope glycoprotein, as an active ingredient, and an adjuvant, as a critical component of the vaccine. The adjuvant is an immunomodulating agent having an iscom-like structure and comprising within the iscom-like structure at least one lipid and at least one saponin, and a pharmaceutically acceptable vehicle. Such a vaccine protects a subject against infection by a Flavivirus.

摘要翻译： 疫苗含有至少一种果蝇细胞分泌的，重组产生的截短的黄病毒包膜糖蛋白形式的活性成分，和佐剂作为疫苗的关键成分。 佐剂是具有类同构结构的免疫调节剂，并且在iscom样结构内包含至少一种脂质和至少一种皂苷以及药学上可接受的载体。 这样的疫苗保护受试者免受黄病毒感染。