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。

公开(公告)号：US06416763B1

公开(公告)日：2002-07-09

申请号：US09143077

申请日：1998-08-28

申请人： Michael McDonell ,  Iain Peters ,  Beth-Ann Coller

发明人： Michael McDonell ,  Iain Peters ,  Beth-Ann Coller

IPC分类号： A61K3912

CPC分类号： C07K14/005 ,  A61K39/12 ,  A61K2039/525 ,  A61K2039/55566 ,  A61K2039/55577 ,  C12N2770/24122 ,  C12N2770/24134 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394 ,  Y02A50/396

摘要： The recombinant expression and secretion from eucaryotic host cells, particularly Drosophila cells, of Flavivirus nonstructural (NS) protein, particularly NS1, is useful in combination with Flavivirus truncated envelope (E) protein to protect a host subject from infection and disease from Flavivirus species. Further, NS1 is useful as a diagnostic of flaviviral infection. Compositions of truncated flaviviral envelope protein and flaviviral nonstructural protein induce high titer virus neutralizing antibodies believed to be important in protection against flaviviral infection and which are useful in diagnosis of infection by the virus.

摘要翻译： 黄病毒非结构（NS）蛋白，特别是NS1的真核宿主细胞，特别是果蝇细胞的重组表达和分泌可与黄病毒截短的包膜（E）蛋白结合用于保护宿主受体免受黄病毒种的感染和疾病。 此外，NS1可用作黄病毒感染的诊断。截短的黄病毒包膜蛋白和黄病毒非结构蛋白的组成诱导高滴度病毒中和抗体，其被认为在防止黄病毒感染中是重要的，并且其可用于诊断病毒感染。