Provided herein are compositions and methods for generating an immunogenic response in humans. Such compositions include an immunogenic biological agent encompassed by (ii) an agent that directs delivery of the immunogenic biological agent to the ileum of the human, wherein agent (ii) is an enteric coating (e.g., Eudragit®) that has a threshold pH 5.8-6.8. Further provided are methods for designing such compositions, e.g., for vaccines.

Provided is a chimeric hemagglutinin (HA) protein including an HA1 subunit and an HA2 subunit, in which the HA1 subunit is composed of a first domain derived from a parental HA1 subunit of a first subtype influenza virus and a second domain derived from a parental HA1 subunit of a second subtype influenza virus. The chimeric HA protein has improved thermal stability and can be used in a vaccine composition for preventing influenza virus infection. Also provided is a method of inducing an immune response against an influenza virus in a subject in need thereof that includes administering the chimeric HA protein to the subject, thereby conferring protection against the influenza virus infection on the subject.

A method of identification and elimination of immunodominant epitopes to elicit a response to secondary epitopes, especially conserved structures, is described, and applied to influenza haemagglutinin (HA). Identification of the primary epitopes in (HA), and replacement of amino acids having high LODrps with corresponding low LODrps amino acids produces an HA molecule which induces antibody responses to conserved HA residues. Modified HA molecules induce a broadly neutralizing vaccine.

A method of identification and elimination of immunodominant epitopes to elicit a response to secondary epitopes, especially conserved structures, is described, and applied to influenza haemagglutinin (HA). Identification of the primary epitopes in (HA), and replacement of amino acids having high LODrps with corresponding low LODrps amino acids produces an HA molecule which induces antibody responses to conserved HA residues. Modified HA molecules induce a broadly neutralizing vaccine.

This invention discloses a method of increasing production of virus-like particles comprising expressing an avian influenza matrix protein. The invention also comprises methods of making and using said VLPs.

The present invention is directed to a polymeric carrier cargo complex, comprising as a cargo at least one nucleic acid molecule and as a preferably non-toxic and non-immunogenic polymeric carrier disulfide-crosslinked cationic components for use as an immunostimulating agent or as an adjuvant, wherein the polymeric carrier cargo complex is administered in combination with at least one second nucleic acid molecule, which encodes a protein or peptide. The inventive polymeric carrier cargo complex administered in combination with the second nucleic acid molecule allows for both efficient transfection of nucleic acids into cells in vivo and in vitro and/or for induction of an innate and/or adaptive immune response, preferably dependent on the nucleic acid to be transported as a cargo and on the second nucleic acid molecule. The present invention also provides pharmaceutical compositions, particularly vaccines, comprising the inventive polymeric carrier cargo complex and the second nucleic acid molecule, as well as the use of the inventive polymeric carrier cargo complex and the second nucleic acid molecule for transfecting a cell, a tissue or an organism, as a medicament, for therapeutic purposes as disclosed herein, and/or as an immunostimulating agent or adjuvant, e.g. for eliciting an immune response for the treatment or prophylaxis of diseases as mentioned herein. Finally, the invention relates to kits containing the inventive polymeric carrier cargo complex and the second nucleic acid molecule, the inventive pharmaceutical composition and/or the inventive vaccine or any of its components in one or more parts of the kit.

The present disclosure relates to a pharmaceutical composition comprising a nucleic acid molecule of an adjuvant, a metal complex stabilizing the nucleic acid molecule, and optionally an immunogen that may be a peptide or a protein, or a composition of stabilizing the nucleic acid molecule of the adjuvant comprising the metal complex. The metal complex interacts with the nucleic acid molecule of the adjuvant and/or the immunogen so as to stabilize such pharmaceutically active ingredients, and induces continuous effectiveness of the active ingredients without degradation.

The present invention relates to a recombinant nonstructural protein 1 (NS 1), a recombinant influenza virus and an immunological composition including the same, as well as a method of treating or preventing a disease or condition caused by or associated with an influenza virus in a subject in need thereof. At least one amino acid residue is mutated or deleted in 4 contiguous amino acid residues of TRAF3-interacting motifs (TIMs) within an effector domain of the recombinant NS 1. A recombinant influenza virus including the recombinant NS1 is comparable to the wild-type influenza virus in virus replication ability, and the recombinant influenza virus can elevate interferon activation of a subject for achieving better immune response and better immunological protection, leading in a method of treating or preventing a disease or condition caused by or associated with an influenza virus in a subject in need thereof.

Disclosed herein are compositions and methods related to mutant viruses, and in particular, mutant influenza viruses. The mutant viruses disclosed herein include a mutant M2 sequence, and are useful in immunogenic compositions, e.g., as vaccines. Also disclosed herein are methods, compositions and cells for propagating the viral mutants, and methods, devices and compositions related to vaccination.

Novel, nanoparticle-based vaccines are provided that elicit an immune response to a broad range of infectious agents, such as influenza viruses. The nanoparticles comprise a heterogeneous population of fusion proteins, each comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to one or more immunogenic portions of a protein from an infectious agent, such as influenza virus. The fusion proteins self-assemble to form nanoparticles that display a heterogeneous population of immunogenic portions on their surface. When administered to an individual, such nanoparticles elicit an immune response to different strains, types, subtypes and species with in the same taxonomic family. Thus, such nanoparticles can be used to vaccinate an individual against infection by different Types, subtypes and/or strains of infectious agents. Also provided are specific fusion proteins, nucleic acid molecules encoding such fusion proteins and methods of using nanoparticles of the invention to vaccinate individuals.