The present disclosure relates to recombinant nucleic acids and uses thereof for developing vaccines.

The invention is directed to immunogens and methods for inducing immune responses, comprising methods for germline B cell stimulation and maturation by reverse engineering of HIV-1 envelopes.

Described herein are methods of preventing or treating a HIV infection comprising administering to a mammal in need thereof, a pharmaceutically effective amount of a CD8+ T cell vaccine composition. Such methods comprising using CD8+ T cells which have been pre-stimulated with at least one HIV epitope, to thereby enhance a CD8+ T cell immune response against HIV in said mammal.

Immunogenic compositions containing a human immunodeficiency virus (HIV) gp140 protein, sorbitol, polysorbate 20, and histidine buffer are described. The described immunogenic compositions are advantageous in that they are stable at refrigerated temperature for extended periods of time, and are compatible with an adjuvant. Also described are methods of using the immunogenic compositions to induce an immune response against an HIV in a subject. The immunogenic compositions can be administered alone, or in combination with one or more additional HIV antigens, or one or more adenovirus vectors encoding the one or more additional HIV antigens.

The invention relates to HIV-1 envelope polypeptides comprising the consensus envelope of SEQ ID NO: 35, compositions comprising these envelopes and methods for using same.

The present invention provides novel scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.

The invention relates to germline-targeting designs, stabilization designs, and/or combinations thereof, of proteins designed with modified surfaces helpful for immunization regimens, other protein modifications and/or development of nanoparticles, methods of making and using the same, and to (a) germline-targeting priming or boosting/shepherding immunogens to initiate or guide maturation of VRC01-class responses (b) PCT64/PG9-germline-targeting designs (c) BG18-germline-targeting designs or boosting/shepherding immunogens to initiate or guide maturation of BG18-like responses, and/or (d) trimer stabilization and presentation in a membrane-bound format.

The present invention relates to methods and compositions for the stimulation of immune responses. Specifically, the present invention provides methods of inducing an immune response to human immunodeficiency virus (HIV) in a subject (e.g., a human subject) and compositions useful in such methods (e.g., a nanoemulsion comprising HIV or antigenic portion thereof).

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.