We have recently developed a novel DC-targeting vaccine platform using Ebola glycoprotein (EboGP) DC-targeting domain-based fusion protein technology. Here, we will use this technology to generate universal vaccines against Influenza A by fusing a DC-targeting/activation domain (EboGPAM), derived from EboGP to I) a tetrameric conserved extracellular domain of M2 (M2e) of Influenza A strains from human, birds, and swine; 2) the conserved stalk regions (HAcs) of HA and an M2 polypeptide from H5N1 strain; and 3) the HA head regions polypeptides (HA.sub.H5-1-3) derived from H5N1, H1 N1 and H3N2 strains.

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.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

Compositions and methods are disclosed for treating and/or preventing viral infections and related pathologies (e.g., Coronavirus and Ebola virus infections and related pathologies). Composition includes those with modified viral glycoproteins, wherein one or more portions of the modified viral glycoproteins are modified to comprise an antigen. Variously, the antigen can include a Coronavirus antigen or an Ebola virus antigen.

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.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilized by sequence modifications and optimized for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilization and translational efficiency of modified mRNA of the invention.

Provided are an Ebola virus envelope glycoprotein (that is GP protein) codon optimized nucleotide sequence, a human replication deficient recombinant adenovirus capable of expressing the nucleotide sequence, and applications in preparing a vaccine for preventing Ebola virus diseases. The nucleotide sequence takes a replication deficient 5 type adenovirus that is lack of E1 and E3 in a combined mode as a vector. HEK293 cells that integrate adenovirus E1 genes serve as a packaging cell line, and carried protective antigenic genes are codon optimized Zaire type Ebola virus Makona strain envelope glycoprotein genes. After the envelope glycoprotein genes are optimized by codon, the expression level in transfection cells is obviously improved.

The present disclosure relates to mRNA, self-replicating RNA, and temperature-sensitive, self-replicating RNA encoding a coronavirus nucleocapsid protein or an influenza virus nucleocapsid protein in operable combination with a mammalian signal peptide. The present disclosure relates to mRNA, self-replicating RNA, and temperature-sensitive, self-replicating RNA encoding other viral nucleocapsid protein(s) in operable combination with a mammalian signal peptide. The RNA constructs are suitable for active immunization against a virus in a mammalian subject, such as a human subject.

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.

Stable pre-fusion class I fusion proteins in the pre-fusion conformation, including one or more mutations in the hinge-loop that is present between the base helix and the RR1, are described.