New vaccine compositions comprising a modified antigen bound to the surface of an adjuvant or carrier by electrostatic interactions are disclosed. The antigen of the vaccine composition is presented in a defined orientation on an adjuvant surface such that epitope accessibility is altered and an immune response is redirected toward specific epitopes. In some embodiments the vaccine composition comprises one or more recombinant antigen polypeptides adsorbed to an alum particle. In some embodiments, the recombinant antigen polypeptide comprises a Region of Repetitive Carboxylic Groups (RRC) or a Region of Repetitive Lysyl/Guanidino Groups (RRL).

The present invention relates to monoclonal antibodies and antigen-binding portions thereof that specifically bind to a filovirus (e.g., Marburg virus (MARV)), including antibodies that cross-react with at least two filoviruses. Such antibodies are useful for the prevention and treatment of filovirus infection. The invention also provides pharmaceutical compositions comprising the MARV-binding antibodies, nucleic acid molecules encoding these polypeptides and methods of making these molecules.

The invention relates to vectors comprising two or more homologous nucleotide sequences and methods for generating them. The invention concerns substituting bases in the homologous nucleotide sequences with different bases that do not alter the encoded amino acid sequence. The invention allows for the reduction of intramolecular recombination between homologous nucleotide sequences, in particular in mammalian cells. The invention further relates to nucleotide sequences containing substituted bases.

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.

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.

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.

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.

Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Ebolavirus glycoproteinimmunogens 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 Ebolavirus are disclosed. Method of preventing Ebolavirus and methods of treating individuals infected with Ebolavirus are disclosed. Consensus Ebolavirus proteins are disclosed.

An immunization regimen is provided which involves priming with an E1, E4-deleted adenovirus and boosting with an E1-deleted adenovirus. The second administered adenovirus has a capsid of a serotype which is not cross-reactive with the previously administered adenovirus. Further, a product containing the adenoviruses necessary to perform the immunization regimen is provided.

The present invention relates to methods of modulating an immune response in a subject by using a binding protein (e.g., an antibody or an antigen-binding portion of an antibody) to mask or alter an epitope on an antigen that is administered to the subject. Such methods are useful for inducing an immune response (e.g., production of an antibody) in the subject to a non-immunodominant epitope on the antigen. The invention also encompasses an antigen-binding protein complex comprising at least one binding protein bound to at least one immunodominant epitope on an antigen.