The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

The invention provides a vaccine composition comprising a flavivirus peptide comprising one or more CD8+ T cell epitopes, wherein the peptide is attached to a nanoparticle.

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.

Stable lyophilized immunogenic compositions include inter alia live attenuated recombinant flaviviruses, more preferably live attenuated recombinant dengue viruses, at least one carbohydrate, at least one amino acid and is particularly amenable to rapid freeze-drying treatments wherein, the composition preserves desired characteristics of a virus, including virus viability, immunogenicity and stability. The immunogenic composition is devoid of preservatives, polymers and surfactants. The methods for manufacturing the stable lyophilized immunogenic compositions are also provided.

The present application relates to composition of matter, processes and use of composition of matter relating to flavivirus proteins, peptides, and epitopes, for example, for therapeutic or preventative vaccination against one or more flavivirus serotypes or species, and/or for inducing, enhancing, or sustaining an immune response against at least one flavivirus serotype or species. The flavivirus may be for example the Zika and/or Dengue virus.

Provided herein is an isolated polynucleotide, which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and a polypeptide comprising a coronavirus protein fused to a signal sequence and/or transmembrane domain. The coronavirus protein may be the receptor binding domain of the S1 subunit of coronavirus spike (S) protein. The polynucleotide such as RNA is useful for as a vaccine against coronavirus infection, especially, COVID-19 infection.

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.

Disclosed are modified HCV E2 glycoproteins. Disclosed are modified HCV E2 glycoproteins comprising an antigenic domain D, wherein the modified HCV E2 glycoproteins comprise one or more amino acid alterations in the antigenic domain D, wherein at least one amino acid alteration is a proline substitution. In some aspects, the proline substitution occurs at position 445 based on the amino acid numbering of HCV strain H77. Disclosed are modified HCV E2 glycoproteins comprising an antigenic domain A, wherein the antigenic domain A comprises an N-glycan sequon substitution. In some aspects, the N-glycan sequon substitution results in an Asn-Xaa-Ser or Asn-Xaa-Thr substitution, wherein Xaa is any amino acid except proline. Also disclosed are methods of using the disclosed modified HCV E2 glycoproteins, such as methods of inducing an immune response in a subject, methods of treating a subject, and methods of increasing antigenicity of HCV E2 glycoprotein.

The invention provides a vaccine composition comprising a flavivirus peptide comprising one or more CD8+ T cell C1 epitopes, wherein the peptide is attached to a nanoparticle.

The present application relates to an inhibitor of fusion between a viral membrane from an enveloped virus and a cell membrane, where the viral membrane comprises a fusion mediating protein including a C-terminal peptide. The inhibitor comprises the C-terminal peptide of the fusion mediating protein from an enveloped virus and tocopherol or a derivative or pharmaceutically acceptable salt thereof attached to the C-terminal peptide. Also disclosed is a pharmaceutical composition including the inhibitor as well as methods of inhibiting viral fusion, blocking viral spread, and preventing or treating viral infection, with the inhibitor or pharmaceutical composition.