Isolated monoclonal antibodies which bind to Zika virus envelope protein and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic and diagnostic methods for using the antibodies.

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from an attenuated or wild-type dengue serotype 2 virus (DENV-2), and a portion of a prM signal sequence, a prM protein and at least a portion of an envelope (E) protein from a Zika virus (ZIKV) are described. Also described are immunogenic compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV.

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.

The present invention is directed to a dengue virus chimeric polyepitope composed of fragments of non-structural proteins and its use in an immunogenic composition against dengue virus infection. The present invention provides means, in particular polynucleotides, vectors, cells and methods to produce vectors expressing said chimeric polyepitopes, in particular vectors consisting of recombinant measles virus (MV) particles. The present invention also relates to the use of the recombinant MV particles, in particular under the form of a composition or of a vaccine, for the prevention and/or treatment of a dengue virus infection.

Transcriptional units encoding Zika virus (ZIKV) premembrane (prM) and envelope (E) proteins, which upon translation form Zika virus-like particles (VLPs), are described. Use of the transcriptional units and VLPs in three different ZIKV vaccine platforms is described. Immunoassay-based detection methods using ZIKV VLPs are described for the diagnosis of ZIKV infection.

The disclosure provides materials in the form of flavivirus variants that each encode a Non-Structural Protein-1 (NS1) variant, wherein the coding region is a chimera of at least two different NS1 coding regions, or wherein the coding region has at least one mutation in a codon of a canonical Asn-Xxx-Ser/Thr N-linked glycosylation site, wherein Asn is asparagine, Xxx is any amino acid, and Ser/Thr is either serine or threonine, or wherein the coding region is both a chimera and has at least one mutation in a codon of a canonical N-liked glycosylation site, wherein Asn is asparagine, Xxx is any amino acid, and Ser/Thr is either serine or threonine. The disclosure also provides methods of using such flavivirus variants to inhibit the transmission of infectious flavivirus.

The invention relates to isolated recombinant analogues of flavivirus E-protein fusion loops comprising at least one glycosylation site for an N-linked glycan that is not present in the natural flavivirus E-protein fusion loop sequence, wherein the at least one glycosylation site is an N-linked glycosylation sequon (Asn-X-Ser/Thr) and the Asn (N) residue of the sequon occupies any of positions 98-110 (SEQ ID NO: 1) (DRGWGNGCGLFGK) of the natural flavivirus E-protein fusion loop amino acid sequence, wherein X is any amino acid residue except proline and Ser/Thr denotes a serine or threonine residue.

Described herein are processes for purifying infectious Zika virus particles and uses of protamine in such processes.

Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.

Compounds useful as components of immunogenic compositions for the induction of an immunogenic response in a subject against viral infection, methods for their use in treatment, and processes for their manufacture are provided herein. The compounds comprise a nucleic acid construct comprising a sequence which encodes a Zika virus antigen. A particular embodiment is a nucleic acid-based vaccine construct encoding a polypeptide comprising a full-length Zika virus prME antigen. A particular embodiment is a self-replicating RNA molecule comprising a construct encoding a polypeptide comprising a full-length Zika virus prME antigen.