The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus, or arenavirus. 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 Ebolavirus (such as a member of species Zaire ebolavirus), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus), or a member of genus Arenavirus (such as a member of species Lassa 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 ebolavirus, Marburgvirus, or arenavirus.

The disclosure relates to compositions, assays, methods and kits comprising one or more amino acid sequences of a filovirus protein, or a fragment thereof, which find use in the detection of a filovirus infection and/or the presence of antibodies specific for a filovirus in a biological sample.

Disclosed is a stable immunogenic composition capable of eliciting a robust and durable immune response, comprising at least one antigen consisting of a filovirus glycoprotein and at least one nano-emulsion adjuvant which are co-lyophilized and can be reconstituted immediately prior to use. Also disclosed is a vaccine composition comprising at least two antigens, wherein each antigen is specific to a different genus of filovirus and which also comprises at least one nano-emulsion adjuvant.

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.

Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Marburgvirus filovirus glycoprotein immunogens. Immunomodulatory methods and methods of inducing an immune response against Marburgvirus are disclosed. Method of preventing infection by Marburgvirus and methods of treating individuals infected with Marburgvirus are disclosed. Consensus Marburgvirus filovirus glycoprotein immunogens are disclosed.

Compositions and methods are described for generating an improved effective immune response against an immunogen in humans. The enhanced immune response, is obtained by using an MVA vector as a prime and an adenovirus vector as a boost and is characterized by a high level of antibody response specific to the immunogen, and an enhanced cellular immune response. The compositions and methods can be used to provide a protective immunity against a disease, such as an infection of one or more subtypes of Ebola and Marburg filoviruses, in humans.

The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein derived from the glycoprotein (GP) and/or the matrix protein 40 (VP40) and/or the nucleoprotein (NP) of a virus of the genus Ebolavirus or Marburgvirus or a fragment, variant or derivative thereof. Additionally, the present invention relates to a composition comprising a plurality of mRNA sequences comprising a coding region, encoding at least one antigenic peptide or protein derived from the glycoprotein (GP) and/or the matrix protein 40 (VP40) and/or the nucleoprotein (NP) of a virus of the genus Ebolavirus or Marburgvirus or a fragment, variant or derivative thereof. Furthermore it also discloses the use of the mRNA sequence or the composition comprising a plurality of mRNA sequences for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of Ebolavirus or Marburgvirus infections. The present invention further describes a method of treatment or prophylaxis of Ebolavirus or Marburgvirus infections using the mRNA sequence.

The present invention relates to an improved filovirus vaccine comprising a recombinant modified vaccinia virus Ankara-based (MVA-based) vaccine against filovirus infection and to related products, methods and uses. Specifically, the present invention relates to genetically engineered (recombinant) MVA and FPV vectors comprising at least one heterologous nucleotide sequence encoding an antigenic determinant of a Marburg virus (MARV) or Ebola virus glycoprotein. Specifically, the invention relates to recombinant MVA comprising Ebola virus glycoprotein and virion protein 40. The invention also relates to products, methods and uses thereof as well as prime/boost regimens of MVA and genetically engineered (recombinant) FPV, e.g., suitable to induce a protective immune response in a subject.

The present invention provides compositions, vaccines and methods for inducing protective immunity against filovirus infection, particularly protective immunity against infection of one or more subtypes of Ebola viruses and Marburg virus.

The present invention relates to a nucleotide sequence as shown in SEQ ID NO: 1 for encoding a Marburg virus envelope glycoprotein, and to a human replication-deficient recombinant adenovirus capable of expressing the nucleotide sequence and a preparation method therefor, as well as an application thereof in the preparation of a vaccine against Marburg virus disease. The vaccine uses an E1 and E3 deleted replication-deficient human type-5 adenovirus as a vector, and HEK293 cells integrating an adenovirus E1 gene as a packaging cell line, and a protective antigen gene carried is a codon-optimized Marburg virus Angola strain envelope glycoprotein gene. After codon optimization of the envelope glycoprotein gene, significant expression of envelope glycoprotein can be detected in transfected cells.