Compounds, compositions and methods are provided for the inhibition of ENPP1. Aspects of the subject methods include contacting a sample with a cell impermeable ENPP1 inhibitor to inhibit cGAMP hydrolysis activity of ENPP 1. Also provided are vaccine compositions and methods relate thereto. Aspects of the methods include administering to a subject an effective amount of a cell impermeable ENPP1 inhibitor to inhibit the hydrolysis of cGAMP in combination with a vaccine.

The present invention relates to pharmaceutical compositions comprising a mixture of a specific HIV antigen and a non-pathogenic living bacterium. Said specific HIV antigen comprises one or more epitopes from Gag and/or Pol proteins and is preferably under a particulate form. Said bacterium is preferably Lactobacillus plantarum. These compositions are useful for preventing and/or treating an HIV disease in humans.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

Antibodies and method of making antibodies, either monoclonal or polyclonal wherein said antibodies have dual or multi-specific binding capacity to more than one type of antigenic epitope. The antibodies have simultaneous or independent recognition subsites to each of the epitopes. Antigenic epitopes include lipids, peptides, proteins, amino acid sequences, sugars and carbohydrates. Monoclonal antibodies and a method of making monoclonal antibodies of the invention include monoclonal antibodies that are broadly neutralizing to HIV-1 or other envelop viruses wherein the monoclonal antibody has subsites that simultaneously recognize protein and lipid epitopes from the virus.

The present invention provides methods for producing HIV-1 nanoparticle vaccines with enhanced immunogenicity. The methods entail (1) enzymatic digestion of glycan chain on the surface of a self-assembling nanoparticle vaccine displaying an HIV-1 Env derived trimer immunogen, or (2) expression of an HIV-1 nanoparticle construct in an expression system lacking normal glycosylation function for human proteins. Also provided in the invention are HIV-1 nanoparticle vaccines produced with the described methods. The invention further provides methods of using the HIV-1 nanoparticle vaccine compositions described herein in various therapeutic applications, e.g., for preventing or treating viral infections.

Immunogenic compositions comprising partially glycosylated viral glycoproteins for use as vaccines against viruses are provided. Vaccines formulated using mono-, di-, or tri-glycosylated viral surface glycoproteins and polypeptides provide potent and broad protection against viruses, even across strains. Pharmaceutical compositions comprising monoglycosylated hemagglutinin polypeptides and vaccines generated therefrom and methods of their use for prophylaxis or treatment of viral infections are disclosed. Methods and compositions are disclosed for influenza virus HA, NA and M2, RSV proteins F, G and SH, Dengue virus glycoproteins M or E, hepatitis C virus glycoprotein E1 or E2 and HIV glycoproteins gp120 and gp41.

Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Disclosed herein are alphavirus vectors that include neoantigen-encoding nucleic acid sequences derived from a tumor of a subject. Also disclosed are nucleotides, cells, and methods associated with the vectors including their use as vaccines.

Provided herein are exosome-anchoring fusion proteins and methods of using the exosome-anchoring fusion proteins for immunization to treat or prevent diseases such as virus infections or cancer.

The disclosure relates to nucleic acids mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids are suitable for use in inducing an immune response to HIV-1 in a human.