The present disclosure is directed to oral vaccine dosage forms and processes for producing the oral vaccine dosage forms. The dosage forms include lipid-based vesicles (e.g., virosomes, liposomes) harboring an immunogenic amount of at least one vaccinal target molecule, with or without adjuvant. Specifically, Applicants discovered a combination of the composition of the liquid virosome concentrates, the composition of the base matrix for the solid dosage form formulation (excluding the virosome concentrate), and the manufacturing conditions for the dosage forms that can produce a freeze dried sublingual dosage form having physical robustness, particle and antigen integrity and stability.

Methods of preparing plant-derived virus like particles (VLPs) are provided. The method may comprise obtaining a plant, or plant matter comprising apoplast-localized VLPs, producing a protoplast/spheroplast fraction and apoplast fraction from the plant or plant matter, and recovering the apoplast fraction. The apoplast fraction comprises plant-derived VLPs. Alternatively, VLPs may be obtained from plant or plant matter comprising plant-derived VLPs by digesting the plant matter using a cell wall degrading enzyme composition to produced a digested fraction. The digested fraction is filtered to produced a filtered fraction, and the plant-derived VLPs are recovered from the filtered fraction.

A method for synthesizing influenza virus-like particles (VLPs) within a plant or a portion of a plant is provided. The method involves expression of influenza HA in plants and the purification by size exclusion chromatography. The invention is also directed towards a VLP comprising influenza HA protein and plant lipids. The invention is also directed to a nucleic acid encoding influenza HA as well as vectors. The VLPs may be used to formulate influenza vaccines, or may be used to enrich existing vaccines.

Provided, herein, in certain embodiments are virus-like particles such as synthetic enveloped VLPs or synthetic membrane VLPs. In some embodiments, the VLPs comprise a lipid bilayer. In some embodiments, the VLPs comprise a purified antigen anchored to the lipid bilayer. Some embodiments relate to vaccines comprising the VLP, methods of using the vaccine, and methods of making the vaccine or VLP.

The present invention provides, among other things, a novel and improved method for generating “mosaic” influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered H1N1 influenza hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple H1N1 viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

Described herein are compositions of and methods of making vaccines which can provide broad serological reactivity an inverse dose response, and a swarm effect.

Methods of preparing plant-derived proteins or suprastructure proteins, are provided. The method may comprise obtaining a plant, or plant matter comprising apoplast-localized proteins, or suprastructure proteins, producing a protoplast/spheroplast fraction and apoplast fraction from the plant or plant matter, and recovering the apoplast fraction. The apoplast fraction comprises plant-derived proteins or suprastructure proteins. Alternatively, the proteins, or suprastructure proteins, may be obtained from plant or plant matter comprising plant-derived proteins or suprastructure proteins, by digesting the plant matter using a cell wall degrading enzyme composition to produced a digested fraction. The digested fraction is filtered to produced a filtered fraction, and the plant-derived proteins or suprastructure proteins, are recovered from the filtered fraction.

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 provides, among other things, modified recombinant HA polypeptides with broadened immunogenic profile that extends coverage to antigenically distinct influenza strains and methods of making and using the same.

The present invention relates to methods of rescue and/or propagation of paramyxovirus species, particularly wherein both rescue and propagation are carried out in the same cell type; i.e., without the use of helper cells for viral rescue. The paramyxoviruses produced by the disclosed methods may encompass wild-type viruses, chimeric viruses, recombinant viruses or engineered viral products such as virus like particles (VLP). Viruses and/or viral products produced in the method according to the current invention are suitable for medical or veterinary use in such applications as treating or preventing infectious diseases, particularly avian paramyxovirus and human respiratory virus infections, and cancer treatment.