A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.

A flavivirus virus-like particle and methods of making and using that particle, and antibodies raised to a plurality of those particles, arc provided.

A flavivirus Envelope Dimer Epitope (EDE) and isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus are provided. The dimer is: covalently stabilized with at least one disulphide inter-chain bond or one sulfhydryl-reactive crosslinker between the two sE monomers, and/or by being formed as a single polypeptide chain, and/or by linking the two sE monomers through modified sugar, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. The dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from DENV-1, DENV-2, DENV-3, DENV-4, Zika and/or other flavivirus.

The present disclosure is directed to antibodies binding to and neutralizing Zika virus and methods for use thereof.

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 invention generally relates to the development of immunogenic compositions comprising a DNA copy of at least one live attenuated plus-sense single-stranded RNA virus genome, such as the genome of a live-attenuated Zika vims (ZIKV), Japanese encephalitis virus (JEV) or yellow fever vims (YFV). The immunogenic compositions can be used for treating or conferring protective immunity against diseases related to plus-sense single-stranded RNA viruses, e.g. for affording prolonged immunoprotection against such viruses and protective immunity is conferred at low diseases, e.g., as low as 300 or 500 ng after administration of a single pLAV dosage.

The compositions and methods are described for generating an immune response to a flavivirus such as Zika virus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Flavivirus (such as a member of species Zika virus), in the 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 an infection caused by Flavivirus.

An aspect of the present invention is related to nucleic acid constructs capable of expressing a Zika antigen that elicits an immune response in a mammal against Zika virus, and methods of use thereof. Additionally, there are DNA plasmid vaccines capable of generating in a mammal an immune response against a Zika virus, comprising a DNA plasmid and a pharmaceutically acceptable excipient, and methods of use thereof. The DNA plasmid is capable of expressing a Zika antigen in a cell of the mammal in a quantity effective to elicit an immune response in the mammal that is cross reactive against all Zika strains.

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 invention relates to a single 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.