Disclosed are methods and compositions for at least preventing, treating, inhibiting, or attenuating an Ebola virus infection of a subject. The methods comprise administering an effective amount of a composition as described herein to the subject thereby at least preventing, treating, inhibiting, or attenuating the Ebola virus infection of the subject. The compositions comprise a therapeutic double-stranded RNA (tdsRNA) and additional optional components such as an Ebola antigen.

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.

In this application is described a method for preparing nano-VLP composition, thereby permitting purification using chromatography and filtration. The nano-VLP composition has a more uniform size range of filovirus particles, roughly 230 nm diameter, allowing ease of manipulation of the composition, while retaining GP conformational integrity and the antigenic effectiveness of the vaccine. Additionally, the nano-VLP can be lyophilized without loss of nano-VLP structure, or GP immunogenicity. Lyophilized nano-VLP have greatly enhanced thermostability, allowing the creation of a filovirus nano-VLP vaccine without a cold chain requirement.

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.

We have developed a series of Ebola vims envelope glycoprotein (EboGP)-based chimeric fusion proteins that are still able to maintain an efficient EboGP-mediated virus entry in various cell types including human antigen-presenting cells (APCs) while presenting large viral polypeptides, such as HIV Env v3-v5 domain (as large as 241 aa), at the apex and the sides of each EboGP monomer to elicit robust host immune responses. This invention demonstrates the feasibility of an EboGP-based chimeric fusion technology as a novel vaccine approach against different microbial pathogens, including that in human and animals, and against cancers.

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.

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.

The invention provides a vaccine comprising a recombinant biologically contained filovirus and methods of making and using those viruses.

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.

We have developed a series of Ebola vims envelope glycoprotein (EboGP)-based chimeric fusion proteins that are still able to maintain an efficient EboGP-mediated virus entry in various cell types including human antigen-presenting cells (APCs) while presenting large viral polypeptides, such as HIV Env v3-v5 domain (as large as 241 aa), at the apex and the sides of each EboGP monomer to elicit robust host immune responses. This invention demonstrates the feasibility of an EboGP-based chimeric fusion technology as a novel vaccine approach against different microbial pathogens, including that in human and animals, and against cancers.