The present invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a Filovirus glycoprotein is located at the intergenic region between the E and NS1 gene of said Flavivirus, such that a chimeric virus is expressed, characterised in that the encoded sequence C terminally of the E protein of said Flavivirus and N terminally of the signal peptide of the NS1 protein of said Flavivirus comprises in the following order: a further signal peptide of a Flavivirus NS1 protein, a filovirus glycoprotein wherein the N terminal signal peptide is absent, a TM domain of a flaviviral E protein.

Filovirus glycoprotein mutations that stabilize the trimeric form of the glycoprotein are provided. The Filovirus glycoproteins have certain amino acid substitutions at specified positions in the glycoprotein sequence. The Filovirus glycoproteins described herein have an improved percentage of trimer formation and/or an improved trimer yield as compared to a Filovirus glycoprotein that does not have one or more of the indicated amino acid substitutions. Also provided are nucleic acid molecules and vectors encoding the Filovirus glycoproteins, as well as compositions containing the Filovirus glycoproteins, nucleic acid, and vectors.

Disclosed are chimeric polypeptides based on viral membrane fusion proteins. More particularly, the present invention discloses chimeric polypeptides that comprise a virion surface exposed portion of a viral fusion protein and a heterologous structure-stabilizing moiety, and to complexes of those chimeric polypeptides. The present invention also discloses the use of these complexes in compositions and methods for eliciting an immune response to a fusion protein of an enveloped virus, or complex of the fusion protein, and/or for treating or preventing an enveloped virus infection. The present invention further discloses the use of the heterologous structure-stabilizing moiety for oligomerizing heterologous molecules of interest.

Methods for identifying optimized antigenic pathogen polypeptides capable of inducing a broadly neutralizing immune response, and associated T-cell responses, to a pathogen are described, as well as nucleic acid sequences encoding such polypeptides. Methods for determining whether a broadly neutralizing immune response is induced in a subject following immunization with an optimized antigenic pathogen polypeptide, or a nucleic acid encoding the optimized pathogen polypeptide, are also described. Nucleic acid molecules, polypeptides, vectors, cells, fusion proteins, pharmaceutical compositions, and their use as vaccines against pathogens, especially against emerging or re-emerging pathogens (particularly RNA viruses), are also described.

Isolated peptides comprising one or more antigenic sites of filovirus glycoprotein and methods of their use and production are disclosed. Nucleic acid molecules encoding the peptides are also provided. In several embodiments, the peptides can be used to induce an immune response to filovirus glycoprotein, such as Zaire ebolavirus glycoprotein, in a subject, for example, to treat or prevent infection of the subject with the virus.

Disclosed are chimeric polypeptides based on viral membrane fusion proteins. More particularly, the present invention discloses chimeric polypeptides that comprise a virion surface exposed portion of a viral fusion protein and a heterologous structure-stabilizing moiety, and to complexes of those chimeric polypeptides. The present invention also discloses the use of these complexes in compositions and methods for eliciting an immune response to a fusion protein of an enveloped virus, or complex of the fusion protein, and/or for treating or preventing an enveloped virus infection. The present invention further discloses the use of the heterologous structure-stabilizing moiety for oligomerizing heterologous molecules of interest.

Isolated peptides comprising one or more antigenic sites of filovirus glycoprotein and methods of their use and production are disclosed. Nucleic acid molecules encoding the peptides are also provided. In several embodiments, the peptides can be used to induce an immune response to filovirus glycoprotein, such as Zaire ebolavirus glycoprotein, in a subject, for example, to treat or prevent infection of the subject with the virus.

Filovirus glycoprotein mutations that stabilize the trimeric form of the glycoprotein are provided. The Filovirus glycoproteins have certain amino acid substitutions at specified positions in the glycoprotein sequence. The Filovirus glycoproteins described herein have an improved percentage of trimer formation and/or an improved trimer yield as compared to a Filovirus glycoprotein that does not have one or more of the indicated amino acid substitutions. Also provided are nucleic acid molecules and vectors encoding the Filovirus glycoproteins, as well as compositions containing the Filovirus glycoproteins, nucleic acid, and vectors.

The invention provides a vaccine composition comprising a filovirus peptide comprising one or more CD8+ T cell epitopes, wherein the peptide is attached to a nanoparticle

Provided herein are compositions that include an isolated glycosylated polypeptide comprising at least 50 amino acid residues of a surface glycoprotein of a filovirus and a pharmaceutically acceptable carrier. The glycosylated polypeptide corresponds to one or more structural subunits of the glycoprotein. When the compositions are administered to a subject, they stimulate an innate immune response. The response can be stimulated with administration in the absence of an adjuvant. Methods of using the compositions and for their production are also disclosed.