Chimeric flaviviruses engineered to contain a reporter gene and chimeric nucleic acid molecules encoding the chimeric flaviviruses are described. The chimeric flaviviruses further include genomic non-coding regions, non-structural proteins, and at least a portion of a capsid (C) protein from West Nile virus (WNV), and premembrane (prM) and envelope (E) proteins from dengue virus (DENV). Diagnostic assays that utilize chimeric West Nile/dengue viruses are further described.

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.

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.

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.

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.

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.

The present disclosure relates to Zika vaccines. In certain embodiments, this disclosure relates to vaccine compositions for use in methods of protecting a human subject against Zika disease or infection, wherein said composition comprises a vaccinal for Zika such as a live attenuated or inactivated chimeric Zika virus; live attenuated Zika virus; an inactivated Zika virus; a replication-defective pseudo-infectious Zika virus; a Zika virus-like particle (VLP), a Zika protein or combinations thereof. In certain embodiments, the Zika vaccinal comprises or encodes altered polypeptide sequences disclosed herein.

The disclosure discloses a group of therapeutic genes and their products, which activate specific immune T cells to elevate systemic immune response to treat solid cancer. The active ingredients of the immune gene-drugs are the human genes mainly encoding T cell-targeting molecules, so-called T cell costimulator. The expressed costimulators specifically activate a variety of T cells through receptor-ligand interaction to induce a systemic immune response. These therapeutic gene products, which normally produce in B lymphocytes, are grafted into tumor cells through vectors since the therapeutic effects of the gene drugs rely on the expressed functional proteins on the tumor cell surface. The transplantation of the therapeutic genes into the tumor is performed by DNA plasmids and/or replicable gene vectors that are viruses.

The present invention relates to a yellow fever (YF) vaccine for use in a method for inducing a protective immune response against yellow fever, wherein said method comprises concomitantly administering said yellow fever vaccine to a human subject together with a tetravalent dengue vaccine which comprises a live attenuated dengue virus of each of serotypes 1 to 4. This invention also pertains to a tetravalent dengue vaccine which comprises a live attenuated dengue virus of each of serotypes 1 to 4 for use in a method of inducing a protective immune response against yellow fever, wherein said method comprises concomitantly administering said tetravalent dengue vaccine to a human subject together with a yellow fever (YF) vaccine.

Chimeric flaviviruses engineered to contain a reporter gene and chimeric nucleic acid molecules encoding the chimeric flaviviruses are described. The chimeric flaviviruses further include genomic non-coding regions, non-structural proteins, and at least a portion of a capsid (C) protein from West Nile virus (WNV), and premembrane (prM) and envelope (E) proteins from dengue virus (DENV). Diagnostic assays that utilize chimeric West Nile/dengue viruses are further described.