The present disclosure associates to a modified and expressed virus-like particles. Particularly, the virus-like particle is capable of eliciting immune response in a mammal upon administrating a pharmaceutically efficient dosage to the mammal. The virus-like particle comprises a modified form of M and E structural proteins of flavivirus. Further, the virus-like particle comprises an amino acids sequence substantially corresponding to a sequence setting forth in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 or SEQ ID NO. 4, wherein conserved and internally located His at multiple positions of the M and E proteins are substituted with uncharged residues, and other secretion-enhancing substitutions are introduced.

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.

Provided are surprisingly effective methods for inactivating pathogens, and for producing highly immunogenic vaccine compositions containing an inactivated pathogen rendered noninfectious by exposure to a Fenton reagent, or by exposure to a Fenton reagent or a component thereof in combination with a methisazone reagent selected from the group consisting of methisazone, methisazone analogs, functional group(s)/substructure(s) of methisazone, and combinations thereof. The methods efficiently inactivate pathogens, while substantially retaining pathogen antigenicity and/or immunogenicity, and are suitable for inactivating pathogens, or for the preparation of vaccines for a wide variety of pathogens with genomes comprising RNA or DNA, including viruses and bacteria. Also provided are highly immunogenic inactivated vaccine compositions prepared by using any of the disclosed methods, and methods for eliciting an immune response in a subject by administering such vaccine compositions.

Provided herein are methods of use of subunit immunogenic compositions, in particular for the prevention and treatment of Zika vims infections.

A recombinant vesicular stomatitits virus (rVSV) having a Zika virus (ZIKV) envelope (E) gene, a prime boost immunization combination against ZIKV including: (a) a prime vaccine or immunogenic composition comprising a recombinant vesicular stomatitis virus (rVSV) carrying a ZIKV envelope (E) protein, and (b) a boost vaccine or immunogenic composition comprising a rVSV carrying the same ZIKV E protein. The ZIKV gene can be genetically modified to encode a modified ZIKV E protein that elevates glycoprotein synthesis and trigger efficient humoral immune response.

The subject application provides a genetically modified recombinant facultative intracellular invasive bacterial pathogen (RFIIBP) or a recombinant attenuated Salmonella vaccine (RASV) strains encoding Zika virus (ZIKV) antigens. These strains exhibit high immunogenicity, complete safety, and attenuation, and are unable to persist or be shed in an infective or viable form. These RFIIBPs and RASVs also exhibit regulated delayed attenuation in vivo, regulated delayed in vivo synthesis of protective ZIKV antigens. Methods of inducing mucosal, systemic and cellular immunities in hosts are also provided and antibodies produced using the disclosed RFIIBPs and RASVs can comprise neutralizing antibodies against ZIKV that do not crossreact with Dengue virus (DENV).

A flavivirus Envelope Dimer Epitope (EDE) for use in vaccinating an individual against one or more flaviviruses wherein the EDE is a stabilized recombinant flavivirus, optionally dengue virus and/or zika envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, 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, covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4, Zika or other flavivirus; and wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue. The EDE may be a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3, DENV-4 and Zika. An isolated neutralizing antibody or antigen binding fragment thereof directed against the EDE as defined in any one of claims 1 to 29, optionally wherein said antibody or fragment thereof binds the five polypeptide segments of the dengue virus glycoprotein E ectodomain (sE) consisting of the residues 67-74, residues 97-106, residues 307-314, residues 148-159 and residues 243-251, or corresponding residues of the flavivirus or Zika virus glycoprotein E ectodomain, or consisting of Zika PF13 residues 67-77, residues 97-106, residues 313-315, residues 243-253, residue K373 or corresponding residues of the flavivirus glycoprotein E ectodomain, optionally wherein binding is unaffected by presence or absence of dengue N153 (Zika N154) glycan or corresponding residue, for use in a method for prevention and/or treatment of infection by one or more flaviviruses, wherein the one or more flaviviruses is selected from zika virus; zika virus and dengue virus; zika virus and other flaviviruses; flaviviruses other than dengue.

Isolated mutant dengue virus E protein variants are disclosed. The variant comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 1 and has one or more amino acid residue substitutions at position corresponding to Asn8 (N8), Arg9 (R9), Val12 (V 12) and/or Glu13 (E13). The variant may comprise an amino acid sequence that is at least 90% identical to the SEQ ID NO: 1 and lack an infection-enhancing antibody-binding motif comprising the amino acid sequence of SEQ ID NO: 28 at domain I. An isolated nucleic acid sequence encoding the variant, a plasmid expressing the variant, a plasmid expressing a virus-like particle comprising the variant, a DNA vaccine, and a method of detecting the presence of a dengue virus in a biological sample are also disclosed.

Compositions and methods useful for treating and/or preventing a Zika virus infection are provided.

Embodiments herein concern compositions, methods, and uses for inducing an immune response to all four dengue virus serotypes in a child or young adult from about 1 year to about 20 years of age. Some embodiments concern compositions that can include dengue virus chimeras that, either alone or in combination with other constructs, can be used in vaccine compositions against all four dengue virus serotypes. Compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) virus and/or dengue-4 (DEN-4) virus, at various concentrations or ratios to improve protection from infection in children and young adults. In certain embodiments, viruses of the formulations are limited to dengue virus serotypes. Other embodiments concern methods of administering immunogenic compositions against dengue virus that can include chimeric dengue constructs and live, attenuated dengue viruses using single, dual or other regimens.