The application relates to the attenuation of a flavivirus, such as a West Nile Virus (WNV), Zika virus (ZIKV), Japanese Encephalitis Virus (JEV), Dengue Virus (DV), in particular DV4, or Usutu virus. The application notably provides a live and attenuated flavivirus, such as a live and attenuated WNV or ZIKV, comprising a mutated M protein. Said mutated M protein comprises or consists of a sequence, wherein at least the amino acids at positions 36 and 43 in said sequence are mutated. The application also provides embodiments deriving from said live and attenuated flavivirus, such as a WNV or ZIKV, such as nucleic acids, cells, cDNA clones, immunogenic compositions as well as uses and methods.

The present invention includes composition and methods for making multivalent vaccines for immunization against Flavivirus and/or arboviruses including a multivalent Virus Like Particles (VLP) and mixtures thereof, the method comprising: method of making a Flavivirus and/or arboviruses Virus Like Particles (VLP) comprising: inserting two or more nucleic acids that encode at least one Flavivirus protein into a lentiviral backbone vector; generating a lentivirus by transfecting a first cell line with the lentiviral backbone vector and isolating the lentivirus therefrom; transducing a second cell line with the lentivirus; culturing the transduced cell line under conditions in which the multivalent Flavivirus Virus Like Particles (VLP) are released from the cell line; and isolating the Flavivirus Virus Like Particles (VLP) from a culture supernatant, wherein a cell line makes a virus-specific VLP, and the VLPs are purified and then mixed in different combinations to make the multivalent vaccine.

The invention relates to a method for preventing dengue disease and hepatitis A in a subject or subject population by simultaneously administering a unit dose of a dengue vaccine composition and a hepatitis A vaccine on the same day. The unit dose of a dengue vaccine composition includes constructs of each dengue serotype, such as TDV-1, TDV-2, TDV-3 and TDV-4, at various concentrations in order to improve protection from dengue infection.

The present invention relates to a lentiviral vector-based Japanese encephalitis (JE) immunogenic composition. The present invention is directed to a recombinant lentiviral vector expressing the precursor of membrane (prM) and the envelope (E) protein, in particular glycoprotein of a Japanese encephalitis virus (JEV) or immunogenic fragments thereof. The present invention also provides cells expressing the lentiviral vector, uses and methods to prevent a JEV infection in a mammalian host, especially in a human or an animal host, in particular a pig or a piglet, preferably a domestic pig or a domestic piglet.

The present disclosure relates to a pharmaceutical composition comprising a nucleic acid molecule of an adjuvant, a metal complex stabilizing the nucleic acid molecule, and optionally an immunogen that may be a peptide or a protein, or a composition of stabilizing the nucleic acid molecule of the adjuvant comprising the metal complex. The metal complex interacts with the nucleic acid molecule of the adjuvant and/or the immunogen so as to stabilize such pharmaceutically active ingredients, and induces continuous effectiveness of the active ingredients without degradation.

The invention relates to a unit dose of a dengue vaccine composition and methods and uses for preventing dengue disease and methods for stimulating an immune response to all four dengue virus serotypes in a subject or subject population. The unit dose of a dengue vaccine composition includes constructs of each dengue serotype, such as TDV-1, TDV-2, TDV-3 and TDV-4, at various concentrations in order to improve protection from dengue infection.

A polynucleotide comprising the sequence of a live, infectious, attenuated Zika-Japanese encephalitis (JEV) chimeric virus wherein the nucleotide sequence encoding the prME protein of said Zika virus is replaced by a nucleotide sequence encoding the prME protein of a Japanese encephalitis virus, so that said prME protein of said Japanese encephalitis virus is expressed.

Disclosed herein are flavivirus signal peptide mutants useful for enhancing the production and secretion of flavivirus envelope (E) viral proteins or virus-like proteins. Also disclosed herein are methods of vaccinating subjects (e.g., human subjects) against a flavivirus comprising administering an expression vector, wherein the expression vector comprises a polynucleotide, and a fusion polypeptide comprising an engineered signal peptide and a flavivirus envelope (E) protein

Embodiments disclosed herein provide compositions, methods, and uses for recombinant vectors encoding Zika virus (ZIKV) protein subunits, and immunogenic compositions thereof. Certain embodiments provide recombinant vectors encoding ZIKV nonstructural protein 1 (NS 1), and optionally, ZIKV envelope (E) protein and premembrane (prM) protein. Other embodiments provide expression cassettes comprising a promoter operably linked to a polynucleotide that encodes the ZIKV NS 1 protein, and optionally ZIKV E and prM proteins. In some embodiments, the disclosed expression cassettes can be incorporated into a vector to produce a recombinant vector. Also provided are immunogenic compositions comprising one or more recombinant vectors described herein, and methods for inducing an immune response against ZIKV in a subject comprising administering to the subject an immunologically effective dose of an immunogenic composition of the present disclosure.

The present disclosure relates to vaccines and methods for the prevention and treatment of Zika virus infection. Particularly, the present disclosure relates to viral and DNA vaccine vectors which includes or encode for secreted immunogenic peptides of NS1 that eliciting a protective immune response and prevent Zika virus infection of a subject.