The United States of America, As Represented by the Secretary, Department of Health and Human Services

Takeda Vaccines, Inc.

Sanofi Pasteur Inc.

Centers for Disease Control and Prevention

Mahidol University

Center for Disease Control and Prevention

Other

Richard M Kinney

Claire Y H Kinney

Dan T Stinchcomb

Jill Ann Livengood

Bruno Guy

Véronique Barban

Jean Lang

Siritorn Butrapet

Natth Bhamarapravati

Duane J Gubler

Claire Kinney

Jorge E Osorio

O'Neil Wiggan

Eric Thomas Beck

Jill A Livengood

Duane L Gubler

Claire Huang

Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.

Compositions and methods for dengue virus chimeric constructions in vaccines

Compositions and methods for dengue virus chimeric constructs in vaccines

Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural viral proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural genes of a second flavivirus strain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

Avirulent, immunogenic flavivirus chimeras

Embodiments herein report methods, compositions and uses for inducing and/or accelerating viral growth. In certain embodiments, methods, compositions and uses generally relate to copolymer compositions for inducing viral growth, reducing lag time and/or increasing viral plaque size. In other embodiments, methods, compositions and uses of copolymer compositions can be for inducing flaviviral growth, reducing lag in growth and/or increasing plaque size.

Compositions, methods and uses for inducing viral growth

The invention relates to live attenuated VDV1 (VERO-Derived Dengue serotype 1 virus) strains which have been derived from the wild-type dengue-1 strain 16007 by passaging on PDK and sanitization on Vero cells and nucleic acids thereof. The invention further relates to a vaccine composition which comprises a VDV1 strain.

Dengue serotype 1 attenuated strain

Embodiments herein report methods, compositions and uses for inducing and/or accelerating viral growth. In certain embodiments, methods, compositions and uses generally related to copolymer compositions for inducing viral growth, reducing lag time and/or increasing viral plaque size. In other embodiments, methods, compositions and uses of copolymer compositions can be for inducing flaviviral growth, reducing lag in growth and/or increasing plaque size.

The invention relates to live attenuated VDV2 (VERO-Derived Vaccine Dengue serotype 2) strains which have been derived from the wild-type dengue-2 strain 16681 by passaging on PDK and Vero cells and nucleic acids thereof. The invention further relates to a vaccine composition which comprises a VDV2 strain.

Dengue serotype 2 attenuated strain

The disclosure provides chimeric West Nile/Dengue viruses comprising non-coding regions, non-structural proteins, and a C protein from a West Nile virus and prM and E proteins from a Dengue virus. Also disclosed are methods of using the chimeric viruses in diagnosis of Dengue viral infection, assessment of candidate Dengue virus vaccine efficacy, and production of Dengue prM and E proteins.

Chimeric west nile/dengue viruses

Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural viral proteins of a. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural genes of a secondstrain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

Growing community of inventors

Fort Collins, CO, United States of America

Richard M Kinney