Provided herein are methods of incorporating substitutions of specified residues into a filovirus GP in order to increase immunogenicity and/or broaden the cross-reactivity of the protective immune response against other filovirus members. Also provided herein are mutant filovirus GPs comprising such substitutions.

Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus filovirus immunogen including a consensus Marburgvirus filovirus glycoprotein MARV GP immunogen, a consensus Ebolavirus Sudan filovirus glycoprotein SEBOV GP immunogen and a consensus Ebolavirus Zaire glycoprotein ZEBOV GP immunogen are disclosed. The coding sequences optionally include operable linked coding sequence that encode a signal peptide. Immunomodulatory methods and methods of inducing an immune response against filovirus, particularly Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire are disclosed. Method of preventing filovirus infection, particularly infection by Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire and methods of treating individuals infected with filovirus infection, particularly infection by Marburgvirus, Ebolavirus Sudan and Ebolavirus Zaire are disclosed. Consensus filovirus proteins are disclosed.

Disclosed herein are virus-like particle (VLP)-based bivalent vaccine compositions. The compositions may comprise a spherical retroviral Group-specific Antigen (Gag) protein core and at least two Ebola glycoproteins. The at least two Ebola glycoproteins may be located at the exterior surface of the spherical Gag protein core, such that the VLP-based vaccine presents at least two Ebola glycoprotein antigens. In one aspect, the at least two Ebola glycoproteins are a Zaire (EBOV) glycoprotein, and a Sudan (SUDV) glycoprotein.

Disclosed herein are virus-like particle (VLP)-based bivalent vaccine compositions. The compositions may comprise a spherical retroviral Group-specific Antigen (Gag) protein core and at least two Ebola glycoproteins. The at least two Ebola glycoproteins may be located at the exterior surface of the spherical Gag protein core, such that the VLP-based vaccine presents at least two Ebola glycoprotein antigens. In one aspect, the at least two Ebola glycoproteins are a Zaire (EBOV) glycoprotein, and a Sudan (SUDV) glycoprotein.

The present invention includes methods of making, and compositions comprising, a uniformly lethal filovirus for outbred small mammals by mutation of the viral genome through serial passages in a small mammal, the method comprising the steps of: obtaining a filovirus strain from a human subject; passing the filovirus strain one or more times by intramuscular injection of one or more filovirus infected tissues into an inbred small mammal until uniform lethality is obtained; passing the filovirus strain in one or more human cell lines; passing the filovirus strain one or more times by intraperitoneal injection of one or more filovirus infected tissues into an outbred small mammal until uniform lethality is obtained; and isolating the uniformly lethal filovirus obtained thereby.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody to an Ebola viral antigen. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating an Ebola virus infection in a subject using said composition and method of generation.

This disclosure relates to scaffolds for inducing antibody responses against antigenic sites. In certain embodiments, this disclosure relates to compositions and methods using a filovirus sGP as a scaffold for inducing antibody responses against antigenic sites in foreign pathogens. In certain embodiments, this disclosure relates to compositions and methods using a filovirus sGP as a scaffold for inducing antibody responses against a virus to produce a viral vaccine.

This disclosure relates to assays for detecting activating antibodies in a sample that are capable of antibody-dependent cell-mediated cytotoxicity. In certain embodiments, this disclosure relates to target cells comprising an antigen on the exterior of the cells and a luciferase inside the cells. In certain embodiments, the antigen is an Ebola-virus glycoprotein. In certain embodiments, this disclosure relates to detecting changes in chemiluminescence of the luciferase as an indication of activating antibodies in a sample capable of cell lysis when mixed with effector cells.

The present application generally relates to the development of a vaccine, or the production of antibodies, capable of providing improved protection against a virus associated with ADE, such as Zika, Dengue and Ebola, based on novel antigenic peptides identified using an informational spectrum method (ISM).

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.