The present disclosure is directed to Compositions comprising a population of multivalent viral particles are described herein. Also described herein are immunogenic compositions comprising a population of multivalent viral particles. Additionally, methods of making a multivalent immunogenic composition comprising a population of multivalent viral particles are described. Lastly, methods of using an immunogenic composition to elicit an immune response in a subject are described herein.

Methods of preparing influenza viruses having altered immunodominant epitopes in HA, e.g., having one or more residues in one or more of antigenic sites A-E in HA altered, and viral vectors, e.g., influenza virus VLPs or non-influenza viruses or VLPs thereof expressing or having influenza HAs with altered immunogenicity as a result of altered immunodominant epitopes therein are provided.

A platform enabling the manufacture of thermostable vaccines by incorporating recombinantly expressed, viral envelope proteins in their native conformation into ether glycerophospholipid nanodisc structures that simulate the natural environment of the envelope proteins. The ether glycerophospholipids include ether-linked hydrophobic side chains, and are derived from or modeled after those found in thermophile bacteria, which increase thermostability, thereby significantly enhancing the vaccine's potency, enabling the production of highly multivalent vaccines incorporating multiple variants of the viral antigen, and improving stability and shelf-life.

Disclosed herein are virus-like particle (VLP)-based bivalent vaccine compositions. The compositions may comprise a spherical retroviral Group-specific Antigen (Gag) protein core and at least two Ebola glycoproteins. The at least two Ebola glycoproteins may be located at the exterior surface of the spherical Gag protein core, such that the VLP-based vaccine presents at least two Ebola glycoprotein antigens. In one aspect, the at least two Ebola glycoproteins are a Zaire (EBOV) glycoprotein, and a Sudan (SUDV) glycoprotein.

Disclosed herein are virus-like particle (VLP)-based monovalent vaccine compositions. The compositions may comprise a spherical retroviral Group-specific Antigen (Gag) protein core and a single Ebola glycoprotein selected from either a Zaire (EBOV) glycoprotein or a Sudan (SUDV) glycoprotein. The Ebola glycoprotein may be incorporated into the surface of the spherical Gag core, wherein said VLP-based vaccine presents a single Ebola glycoprotein antigen.