In one aspect, provided herein is a mosaic influenza virus hemagglutinin (HA) polypeptide comprising an influenza A virus HA ectodomain of an influenza A virus strain HA, wherein the HA ectodomain comprises an HA stem domain of the influenza A virus strain HA and an HA globular head domain of the influenza A virus strain HA, wherein the HA globular head domain of the influenza A virus strain HA has been engineered to comprise one or more amino acid substitutions in one, two, three, four or all of the antigenic sites. In another aspect, provided herein are immunogenic compositions comprising such a mosaic influenza virus HA polypeptide or an influenza A virus comprising such a mosaic influenza virus HA polypeptide. In yet another aspect, provided herein are methods for immunizing a subject against an influenza A vims in a subject comprising administering such an immunogenic composition to the subject.

The present invention relates to the production of modified influenza viral proteins in plants. More specifically, the present invention relates to producing and increasing influenza virus-like particle (VLP) production in plants, wherein the VLPs comprise the modified influenza viral proteins, such as modified influenza hemagglutinin (HA). The HA protein may comprising an amino acid sequence comprising at least one substitution when compared to a corresponding wildtype amino acid sequence. Further provided are nucleic acid encoding the modified HA protein. Furthermore methods of producing an influenza virus like particle (VLP) and methods of increasing yield of production of an influenza virus like particle (VLP) in a plant, portion of a plant, or a plant cell, are also provided.

Provided herein are methods for generating a non-naturally occurring, broadly reactive, pan-epitopic antigen derived from H3 influenza virus that is capable of eliciting a broadly reactive immune response, such as a broadly reactive neutralizing antibody response, against H3 virus following administration to a subject. Also provided is a non-naturally occurring immunogen generated using the methods, and vaccines and compositions comprising the immunogen. Methods of generating an immune response in a subject by administering the immunogen, vaccine, or composition are provided. In particular, the immunogen comprises the hemagglutinin (HA) protein of H3 influenza vims strains.

Provided herein are membrane enveloped virus-like particles (VLPs), and methods of use and synthesis thereof. In particular, yeast-cell-derived VLPs are provided that comprise surface-displayed glycoproteins and/or multiple virally-derived proteins.

Co-administration (for example, immunogenic cocktail compositions and/or prime boost regimens) of computationally optimized H1N1 influenza hemagglutinin (HA) polypeptides is provided. Coadministration of the optimized H1N1 influenza hemagglutinin (HA) polypeptides facilitates synergistic neutralization of viral infection and provides for improved protective immunity (for example, a broad reactive immune response) to diverse and multiple H1N1 influenza virus strains, including both seasonal and pandemic strains.

Disclosed are vaccines capable of achieving protection against RSV while avoiding vaccine-enhanced disease (VED). In particular, vaccine constructs have been molecularly designed and genetically engineered to comprise RSV fusion (F) protein displayed on the surface of a particle, such as a virus-like particles (VLP) and low temperature-prepared split RSV. In some embodiments, the RSV F protein is in a pre-fusion F conformation. Also disclosed a variants and combinations of split RSV and RSV F DNA vaccine with pre-fusion F and enhanced efficacy. In addition, disclosed split RSV vaccines containing pre-fusion F conformation and combination adjuvants MPL and CpG.

The disclosure relates to vaccination compositions, for example, against human papillomavirus, Zika virus, and flu virus. The disclosure also relates to vectors for producing the virus-like particles and immune complex platforms of the vaccination compositions.

The present invention relates to a virus-like particle for preventing or treating toxoplasmosis, comprising influenza virus matrix protein 1; and surface antigen proteins comprising an inner membrane complex, Rhoptry protein 18 and Microneme protein 8 derived from Toxoplasma gondii, and a pharmaceutical composition comprising the same.

A method of producing a virus like particle (VLP) in a plant, and compositions comprising VLPs, are provided. The method involves introducing a nucleic acid comprising a regulatory region active in the plant and operatively linked to a chimeric nucleotide sequence encoding, in series, an ectodomain from a virus trimeric surface protein or fragment thereof, fused to an influenza transmembrane domain and cytoplasmic tail, into the plant, or portion of the plant, the ectodomain is from a non-influenza virus trimeric surface protein and heterologous with respect to the influenza transmembrane domain, and the cytoplasmic tail. The plant or portion of the plant are incubated under conditions that permit the expression of the nucleic acid, thereby producing the VLP. A VLP produced by this method are also provided.

Described herein is the generation of optimized H5N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H5N1 influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on human and avian H5N1 isolates. Provided herein are optimized H5N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.