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 disclosure relates to Zika virus vaccines and immunogenic compositions having one or more antigens from a Zika virus (e.g., a Zika virus clonal isolate, a non-human cell adapted Zika virus, etc.), and methods of treatments and uses thereof

The invention relates to polynucleotides comprising the sequence of a flavivirus preceded by a sequence encoding an N terminal part of a flavivirus Capsid protein, an immunogenic protein, or a part thereof comprising a an immunogenic peptide, and a 2A cleaving peptide, and to the virus encoded by such sequences. The invention further relates to the use of such polynucleotides and viruses as vaccines.

Compositions for protecting subjects from diseases caused by (+) SS RNA virus are described herein. The compositions include (i) a vector containing a DNA encoding a RNA molecule of an infectious (+) SS RNA virus operably linked to a eukaryotic RNA polymerase promoter and a carrier; or (ii) (+) SS RNA viruses obtained from eukaryotic cells transfected with the vector of (i) and a carrier.

Embodiments herein report compositions, methods and uses for dengue-4 (DENV-4) virus constructs. Some embodiments concern a composition that includes, but is not limited to, DENV-4 virus constructs alone or in combination with other constructs, can be used in a vaccine composition to induce an immune response in a subject. In certain embodiments, compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 virus, dengue-2 virus, or dengue-3 virus in combination with DENV-4 virus constructs disclosed herein. In other embodiments, DENV-4 constructs disclosed herein can be combined in a composition with other flavivirus constructs to generate a vaccine against more than one flavivirus. Other embodiments provide methods and uses for DENV-4 virus constructs in vaccine compositions that when administered to a subject induce an immune response in the subject against DENV-4 that is improved by modified constructs compared to other vaccine compositions.

The present invention provides purification strategies for sterically demanding, i.e. large and pleomorphic, infectious virus particles or VLPs derived therefrom, preferably having a measles virus scaffold to yield fractions or compositions with a significantly reduced content of contaminating host cell DNA and a reduced content of further process-related impurities. Further provided are methods of propagating and purifying infectious virus particles having a measles virus scaffold suitable to provide a preparation having a strongly reduced content of contaminating host cell DNA and a reduced content of further process-related impurities for immunogenic or anti-tumor purposes. In addition, immunogenic and vaccine compositions based on the above methods are provided. Finally, there are provided immunogenic or vaccine compositions produced by the disclosed methods, which are suitable for use in immunogenic or prophylactic vaccination treatment of a subject in need thereof.

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.

The present invention provides an efficient process for culturing viruses in the presence of an endonuclease and for producing vaccines, typically from live attenuated viruses, under conditions to reduce the presence of host cell DNA and eliminate the need for a post-harvest DNA digestion step.

The present invention relates to vaccine compositions comprising an attenuated mutant Zika virus. The inventors have introduced mutations at very specific positions that abrogate the N-glycosylation site on the E protein of the epidemic strain which will prevent the generation of auto-antibodies responsible for Guillain-Barre syndrome. The inventors have also produced additional mutations of the virus that result to a dramatic reduction of the cytopathic effects without affecting the capacity to produce high titers of virus. In particular, the present invention relates to an attenuated mutant Zika virus comprising a protein E of the epidemic strain wherein at least one amino acid residue at position 152, 156 or 158 is mutated.

The present invention relates to a method of generating a live attenuated vaccine. The present invention also relates to a live attenuated vaccine produced according to the method of the invention.