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

Sanofi Pasteur Inc.

Centers for Disease Control and Prevention

Mahidol University

Center for Disease Control and Prevention

Other

Claire Y H Kinney

Richard M Kinney

Bruno Guy

Véronique Barban

Jean Lang

Duane J Gubler

Siritorn Butrapet

Natth Bhamarapravati

Eric Thomas Beck

Duane L Gubler

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from an attenuated or wild-type dengue serotype 2 virus (DENV-2), and a portion of a prM signal sequence, a prM protein and at least a portion of an envelope (E) protein from a Zika virus (ZIKV) are described. Also described are immunogenic compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV.

Nucleic acids encoding chimeric dengue/Zika viruses optimized for growth and stability in vero cells

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from West Nile virus (WNV), and a portion of a prM signal sequence, a prM protein and an E protein from Zika virus (VIKV) are described. Also described are compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV. Diagnostic assays that utilize chimeric West Nile/Zika viruses are further described.

Chimeric west nile/zika viruses and methods of use

Disclosed herein are chimericincluding non-coding regions, non-structural proteins, and at least a portion of a C protein from West Nile virus (WNV), and a prM protein and an E protein from Dengue virus (DENV). The DENV may be DEN1 serotype, DEN2 serotype, DEN3 serotype, or DEN4 serotype. Also disclosed herein are compositions and methods for eliciting an immune response in a subject, such as an immune response to one or more DENV serotypes. In particular embodiments, the compositions include one or more inactivated viruses including a WN/DENV chimeric nucleic acid (such as a tetravalent inactivated vaccine including a WN/DEN1 chimera, a WN/DEN2 chimera, a WN/DEN3 chimera, and a WN/DEN4 chimera). The compositions may be administered to a subject to elicit an immune response.

Chimeric West Nile/Dengue viruses and methods of use

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

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

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.

Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural protein 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.

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. The invention further relates to a vaccine composition which comprises a VDV1 strain.

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. The invention further relates to a vaccine composition which comprises a VDV2 strain.

Growing community of inventors

Fort Collins, CO, United States of America

Claire Y H Kinney