Embodiments of immunogens based on the outer domain of HIV-1 gp120 and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to prime an immune response to gp120 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

The present invention provides a combination therapy which relies on a small molecule immune stimulator—cyclic-di-nucleotide (CDN)—that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes) formulated with allogeneic human tumor cell lines engineered to secrete high amounts of GM-CSF. This combination therapy can provide an ideal synergy of multiple tumor associated antigens, DC recruitment and proliferation, coupled with a potent DC activation stimulus.

Provided herein are HIV-1 vaccines comprising a carrier and a population episensus antigen determined using the EpiGraph approach. Also provided are HIV-1 vaccines comprising a carrier, a population episensus antigen, and a tailored antigen. Also provided are methods of designing and producing an HIV-1 vaccine for a subject comprising designing vaccine antigens to optimally cover the diversity within a geographic area using an antigen amino acid sequence generated using the EpiGraph approach, and producing said designed vaccine antigen. Also provided are methods of inducing an effector memory T cell response comprising designing the one or more EpiGraph amino acid sequences, producing a vaccine comprising the one or more EpiGraph amino acid sequences and a vector, and administering the vaccine to a subject. Further provided are methods of treating HIV-1 in a subject comprising administering an effective amount of the described HIV-1 vaccines to the subject in need thereof.

The present invention relates to a vector(s) containing and expressing an optimized HIV EnvF gene, methods for making the same and cell substrates qualified for vaccine production which may comprise vector(s) containing optimized HIV genes.

Compounds, compositions, and methods of treatment and prevention of HIV, including HIV-1 and HIV-2, Dengue, and Chikungunya infection are disclosed. The compounds are TREM-1 inhibitors. Combinations of these TREM-1 inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, JAK inhibitors, macrophage depleting agents, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV, Dengue, or Chikungunya virus in an infected patient.

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.

The present invention relates to immunogenic therapies for the treatment or prevention of a human immunodeficiency virus (HIV) infection or a disease associated with an HIV infection.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.

Compositions, vaccines and methods for inducing an immunity, including a protective immunity, against Human Immunodeficiency Virus (HIV) infection are described. Heterologous vaccine combinations of one or more adenovirus 26 vectors using for priming immunization and an isolated HIV antigenic polypeptide in combination with one or more MVA vectors for boosting immunization induced strong protective immunity against infections by one or multiple clades of HIV.

Disclosed herein are bacteria-based HIV MPER vaccine candidates, as well as bacteria-based candidates for other viruses and for bacteria. The HIV vaccine candidates express MPER-derived antigens on their surfaces using Gram autotransporters. The surface-expressed MPER antigens bind several different MPER-directed anti-HIV Broadly Neutralizing Monoclonal Antibodies. When the bacteria expressing the MPER-derived antigens on their surfaces are used to immunize mice they elicit the production of sera and vaginal wash material that bind the bacteria expressing the MPER antigens. At least one of the bacteria expressing MPER-derived antigens on their surfaces elicits the production of sera with anti-HIV neutralizing activity. Killed whole cell and live Salmonella expressing the MPER derived antigens on their surfaces constitute new approaches to HIV vaccine develop that is plausible and that could ultimately yield an inexpensive, globally appropriate candidate vaccine that could be rapidly produced and deployed largely using currently available technology.