The present invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a Filovirus glycoprotein is located at the intergenic region between the E and NS1 gene of said Flavivirus, such that a chimeric virus is expressed, characterised in that the encoded sequence C terminally of the E protein of said Flavivirus and N terminally of the signal peptide of the NS1 protein of said Flavivirus comprises in the following order: a further signal peptide of a Flavivirus NS1 protein, a filovirus glycoprotein wherein the N terminal signal peptide is absent, a TM domain of a flaviviral E protein.

Disclosed are compositions and methods for the detection of a Flavivirus infection. In some embodiments, the method comprises detecting a recent Flavivirus infection by measuring the amount of anti-NS1 IgG3. In other embodiments, the method comprises detecting a prior Dengue virus infection in a subject previously immunized with a Dengue virus vaccine comprising one or more non-Dengue Flavivirus proteins.

Specific resurfaced Dengue virus glycoprotein subunit E DIII variants and their uses in preventing and treating Dengue virus infection are disclosed. Provided herein are specific resurfaced Zika virus glycoprotein subunit E DIII variants and their uses in preventing and treating Zika virus infection. Multivalent vaccines comprising such resurfaced EDIII variants are also described, in addition to nanoparticle conjugated resurfaced EDIII variants.

Aspects of the disclosure relate to attenuated flaviviruses for use in vaccines and immunogenic compositions. Embodiments include methods for treating or preventing one or more conditions, for example flavivirus infection, using an attenuated flavivirus. In some embodiments, the disclosed methods and compositions involve one or more attenuated flaviviruses that are capable of inducing a protective immune response.

The compositions and methods are described for generating an immune response to an antigen. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens as a fusion product with a viral glycoprotein and matrix protein for generating a protective immune response to a subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat diseases.

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.

Chimeric proteins that comprise one or more amino acid sequences of an insect-specific flavivirus and one or more other immunogenic proteins are provided. The chimeric proteins are suitably capable of forming virus particles. The chimeric protein and/or virus particle may be suitable for delivery to a subject to elicit an immune response to a pathogen and/or for diagnosis or detection of a pathogen. Also provided are nucleic acids and vectors encoding the chimeric proteins, and isolated chimeric insect-specific flaviviruses comprising the chimeric proteins and/or nucleic acids.

The present invention provides for modified Flavivirus such as a modified dengue virus type 1, 2, 3, 4, a combination of these, or a tetravalent combination of these. The modification according to various aspects of the invention results in reduced viral protein expression 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 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 Flaviviruses are used as vaccine compositions to provide a protective immune response.

This disclosure describes a subunit vaccine for a flavivirus, methods of making the vaccine, and methods of using the vaccine. The flavivirus may include, is a mosquito-borne flavivims, for example, Zika virus (ZIKV), dengue virus (DENV), Yellow Fever (YF) virus, and West Nile Virus (WNV). The subunit vaccine may be administered with an adjuvant.

Insecticidal toxins described herein are fused toxin peptides made up of a targeting domain fused to a toxin domain. The targeting peptide generates a specific association with mosquitoes by causing the fused toxin peptide to bind mosquitoes in a way that leads to the insecticidal activity. Transgenic plants described herein are mosquitocidal by expressing an insecticidal toxin protein in nectar that includes a targeting peptide to ensure specificity against mosquitoes. These transgenic plants serve as role models for safety, since they are non-crop plants and specific to one mosquito species.