Disclosed herein are immunogenic compositions or product combinations of engineered hepatitis B and hepatitis D nucleic acids, genes, peptides, or proteins that can be used to illicit an immune response against a hepatitis B and/or hepatitis D infection. Also disclosed are methods of using the immunogenic compositions or product combinations in subjects to generate immune responses against HBV and/or HDV by administering the compositions or combinations with a nucleic acid prime and polypeptide boost approach.

The invention provides a novel fusion protein between flagellin (or portions thereof) and a polypeptide that can form a virus-like particle (VLP) (e.g., hepatitis b core (HBc) protein or portions thereof), where the fusion protein continues to form a VLP in an aqueous environment. The VLPs based on such fusion proteins (e.g., FH VLPs) provide a versatile, highly immunogenic, and safe vaccine carrier capable of displaying or associating a variety of vaccine antigens on VLP surface to elicit potent humoral and cellular immune responses.

The present invention provides a virus-like particle comprising several or more types of HBs-L antigen proteins or a virus-like particle composition comprising a combination of the virus-like particles, for the purpose of provision of an antigen that triggers an immune reaction against HBV of various genotypes.

An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pK.sub.a that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pK.sub.a that is within 1 unit of the pH of step (a).

Polynucleotides encoding hepatitis B virus (HBV) surface antigens, and related combinations are described. Also described are vectors, such as DNA plasmids or viral vectors, expressing the HBV surface antigens, and immunogenic compositions containing the expression vectors. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the immunogenic compositions are also described.

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

Provided are HBV immunogenic polypeptides, polynucleotides encoding such polypeptides, vectors expressing such immunogenic polypeptides for use in eliciting an immune response against HBV; pharmaceutical and immunogenic compositions and kits comprising such polypeptides, polynucleotides or vectors, and methods of use in treating and/or preventing HBV.

Described herein is the use of thin film freeze drying methods with oil-in-water adjuvants to produce improved vaccine compositions. This approach solves several major problems associated with the emulsion-adjuvanted vaccines. Additionally, the developed dry powder compositions have the potential to be administered via non-invasive routes (such as intranasal, pulmonary, transcutaneous with or without microneedles) and be stored at ambient temperatures which significantly reduce the costs of vaccination programs.

A pharmaceutical composition comprising: i) a herpes gE protein, an active fragment of the protein, a variant of the protein, or a mixture of at least two of them; ii) an immunostimulatory composition comprising a saponin and a CpG oligodeoxynucleotide, or consisting of an adjuvant comprising a saponin and a CpG oligodeoxynucleotide. Use of the pharmaceutical composition in the preparation of a medicament for preventing and/or treating a varicella-zoster virus infection and/or a varicella-zoster virus mediated disease. The pharmaceutical composition achieves an unexpected technical effect and can mediate a stronger immune response.

Self-replicating RNA molecules encoding hepatitis B virus (HBV) vaccines are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed self-replicating RNA molecules are also described. Kits comprising the disclosed self-replicating RNA molecules are also described.