The present invention is directed to virus-like particles (VLPs) which display immunogenic peptides of Flavivirus non-structural Protein 1 (NS1) derived from Dengue Virus (DENY), immunogenic compositions and vaccines against Flavivirus infection and related methods of immunizing and/or vaccinating subjects against Flavivirus, especially Dengue infections. The VLPs according to the present invention comprise polypeptide subunits of Dengue NS 1 protein which has been conjugated to the surface of a VLP as described herein, often a VLP derived from a Qbeta (P?) or AP205 bacteriophage.

Modified and expressed virus-like particles are described that are 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 set 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.

Disclosed herein are isolated flavivirus polypeptides comprising an amino acid sequence at least 75% identical to one of SEQ ID NOs: 1-11, or a nucleic acid encoding the polypeptide, or a viral like particle encoding the polypeptide, wherein the polypeptide does not comprise the amino acid sequence of a full-length flavivirus NS1 polypeptide. Methods of using these polypeptides are also disclosed, such as for preventing, treating, or determining the prognosis of a flavivirus infection.

Replicon virus-like particles can be used as flavivirus vaccines.

The present invention provides compositions and methods of use comprising a chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone, which comprises amino acid substitutions that introduce a dengue virus E glycoprotein domain I and domain II hinge region from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.

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 (V12) 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.

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

Provided is a virus like particle comprising one or more zika virus structural proteins, and a composition or vaccine comprising thereof, its use in the prevention or treatment of zika virus disease. The zika virus structural protein contains at least one amino acid alteration in the envelope protein.

The present invention provides a vaccine containing virus-like particles derived from virus particles having an envelope, in which a lipid-component content of the virus-like particles is reduced relative to a lipid-component content of the virus particles.

Disclosed herein is a method for identifying flavivirus cross-reactive epitopes. Also provided are flavivirus E-glycoprotein cross-reactive epitopes and flavivirus E-glycoprotein cross-reactive epitopes having reduced or ablated cross-reactivity (and polypeptides comprising such epitopes), as well as methods of using these molecules to elicit an immune response against a flavivirus and to detect a flaviviral infection.