Provided are methods for rapidly inactivating a pathogen, or for producing a vaccine composition containing an inactivated noninfectious pathogen having retained antigenicity and/or immunogenicity, comprising exposing the pathogen to a chemical inactivating agent (e.g., one or more chemical oxidizing, alkylating or crosslinking agents) in the presence of inorganic polyatomic oxyanions in an amount and for a time sufficient to render the pathogen noninfectious while enhancing retention of pathogen antigenicity and/or immunogenicity relative to that retained by contacting the pathogen with the chemical inactivating agent alone. The methods are broadly applicable to pathogens having RNA or DNA genomes (e.g., including viruses, bacteria, fungi, and parasites). Also provided are vaccine compositions (medicaments) containing a pathogen inactivated by exposure to a an inactivating agent in the presence of elevated concentrations of inorganic polyatomic oxyanions, and methods for eliciting an immune response in a subject by administering the vaccine compositions.

The invention relates to a Zika viral vector vaccine comprising nucleic acid encoding a Zika virus structural antigen, wherein the nucleic acid encoding a Zika virus structural antigen comprises a sequence encoding Zika virus envelope DIII, or part thereof. The invention further relates to a Zika viral vector vaccine in combination with a Chikungunya viral vector vaccine.

Nucleic acid immunisation is achieved by delivering RNA encapsulated within a PEGylated liposome. The RNA encodes an immunogen of interest. The PEG has an average molecular mass of between 1 kDa and 3 kDa. Thus the invention provides a liposome having a lipid bilayer encapsulating an aqueous core, wherein: (i) the lipid bilayer campuses at least one lipid which includes a polyethylene glycol moiety, such that polyethylene glycol is present on the liposome's exterior, wherein the average molecular mass of the polyethylene glycol is between 1 kDa and 3 kDa; and (ii) the aqueous core includes a RNA which encodes an immunogen. These liposomes are suitable for in vivo delivery of the RNA to a vertebrate cell and so they are useful as components in pharmaceutical compositions for immunising subjects against various diseases.

Disclosed herein are single nucleic acid constructs comprising a vector, wherein the vector comprises: a first nucleic acid sequence, wherein the first nucleic acid sequence comprises one or more antigenic sequences of interest, one or more spacer sequences and one or more hydrophobic anchor sequences, operably linked to a first transcriptional control element; a second nucleic acid sequence, wherein the second nucleic acid sequence comprises one or more pathogen-associated molecular pattern (PAMP) sequences operably linked to a second transcriptional control element; a third nucleic acid sequence, wherein the third nucleic acid sequence comprises one or more cell surface receptor binding sequences operably linked to a third transcriptional control element; and a selectable marker. Also described herein, are methods of making the single nucleic acid constructs and methods of administering the single nucleic acid constructs for the treatment or prevention of infections and cancer. Also described herein are cell lines and engineered vesicles made using the single nucleic acid constructs described herein.

Described herein is a method of preventing or treating a disease in a mammalian subject, comprising administering to the subject who is in need thereof an effective dosage of a pharmaceutical composition comprising a virus like particle (VLP) comprising: an alphavirus replicon comprising a recombinant polynucleotide, wherein the polynucleotide comprises a sequence encoding both subunits of a human class II major histocompatibility antigen, a retroviral gag protein, and a fusogenic envelope protein, wherein the VLP does not contain an alphavirus structural protein gene.

Provided are methods for rapidly inactivating a pathogen, or for producing a vaccine composition containing an inactivated noninfectious pathogen having retained antigenicity and/or immunogenicity, comprising exposing the pathogen to a chemical inactivating agent (e.g., one or more chemical oxidizing, alkylating or crosslinking agents) in the presence of inorganic polyatomic oxyanions in an amount and for a time sufficient to render the pathogen noninfectious while enhancing retention of pathogen antigenicity and/or immunogenicity relative to that retained by contacting the pathogen with the chemical inactivating agent alone. The methods are broadly applicable to pathogens having RNA or DNA genomes (e.g., including viruses, bacteria, fungi, and parasites). Also provided are vaccine compositions (medicaments) containing a pathogen inactivated by exposure to an inactivating agent in the presence of elevated concentrations of inorganic polyatomic oxyanions, and methods for eliciting an immune response in a subject by administering the vaccine compositions.

The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.

The present invention relates to a composition including a recombinant nucleic acid sequence that encodes an antibody and a method of generating a synthetic antibody in a subject by administering the composition to the subject. The invention also provides a method of preventing and/or treating disease in a subject using the composition and method of generation.

Provided are surprisingly effective methods for inactivating pathogens, and for producing highly immunogenic vaccine compositions containing an inactivated pathogen rendered noninfectious by exposure to a Fenton reagent, or by exposure to a Fenton reagent or a component thereof in combination with a methisazone reagent selected from the group consisting of methisazone, methisazone analogs, functional group(s)/substructure(s) of methisazone, and combinations thereof. The methods efficiently inactivate pathogens, while substantially retaining pathogen antigenicity and/or immunogenicity, and are suitable for inactivating pathogens, or for the preparation of vaccines for a wide variety of pathogens with genomes comprising RNA or DNA, including viruses and bacteria. Also provided are highly immunogenic inactivated vaccine compositions prepared by using any of the disclosed methods, and methods for eliciting an immune response in a subject by administering such vaccine compositions.

Provided are polynucleotides and viral vectors, e.g., alphavirus or Sindbis viral vectors, encoding multiple, e.g., two or more, epitopes of at least one tumor associated antigen, in which each epitope is separated by a processing or enzyme cleavage site. The encoded epitopes may be the same or different. Also provided are polynucleotides and viral vectors, particularly, alphavirus or Sindbis viral vectors, encoding an immune checkpoint protein, or a ligand binding portion thereof. The immune checkpoint protein or ligand binding portion thereof may be fused to immunoglobulin domains, e.g., an Ig hinge domain and an Ig heavy chain constant domain. Methods of treating subjects having a cancer or tumor, e.g., a TAA-expressing tumor, with the described viral vectors are provided. Treatment of subjects with the vectors, the checkpoint inhibitor molecules and/or other immunomodulatory components, generate an anti-cancer or anti-tumor immune response resulting in increased survivability of tumored subjects and epitope spreading.