The present invention provides for modified Flavivirus such as a modified Zika virus. The modification according to various aspects of the invention results in reduced viral proteins compared to a parent virus, wherein the reduction in expression is the result of recoding one or more regions of the virus. For example, the prM, or envelope (E) region, or the nonstructural protein 3 (NS3) region or both the E and NS3 regions can be recoded. In various embodiments one or more regions are recoded by reducing the codon pair bias or codon usage bias of the protein-encoding sequence. These modified Flavivirus are used as vaccine compositions to provide a protective immune response.

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.

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3 untranslated region (3-UTR) comprising a 30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the 30 mutation deleted from the 3-UTR that removes sequence in the 5 direction as far as the 5 boundary of the TL-3 homologous structure in each of the dengue serotypes 1, 2, 3, and 4, or a replacement of the 3-UTR of a dengue virus of a first serotype with the 3-UTR of a dengue virus of a second serotype, optionally containing the 30 mutation and nucleotides additional to the 30 mutation deleted from the 3-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

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.

The invention features novel attenuated dengue virus mutants and compositions thereof. The invention further features an attenuated dengue virus comprising a proline to leucine change at amino acid position 2343 of non-structural protein 4B (NS4B), wherein the numbering is based upon the prototypic isolate DEN4 Dominica 1981 and the attenuated mutant DEN virus has at least one of the following properties: improved replication in Vero cells or restricted replication in mosquito cells.

Disclosed herein are chimeric flaviviruses including 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.

The present invention relates to a self-amplifying mRNA vaccine, including: a self-amplifying backbone comprising a live attenuated virus having a hairpin loop insert, and wherein at least one or more structural genes of the live attenuated virus have been replaced with at least one target antigen-encoding nucleic acid sequence.

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3 untranslated region (3-UTR) comprising a 30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the 30 mutation deleted from the 3-UTR that removes sequence in the 5 direction as far as the 5 boundary of the TL-3 homologous structure in each of the dengue serotypes 1, 2, 3, and 4, or a replacement of the 3-UTR of a dengue virus of a first serotype with the 3-UTR of a dengue virus of a second serotype, optionally containing the 30 mutation and nucleotides additional to the 30 mutation deleted from the 3-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

The present invention relates to a pharmaceutical composition for prevention or treatment breast cancer, containing a chimeric Zika virus obtained through breast cancer cell passages as an active ingredient.