The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines against infectious diseases such as HIV.

Disclosed are compositions and virus-like particles (VLPs) self-assembled from the expression of human immunodeficiency virus (HIV) Gag protein and a fragment of gp41 protein containing its N-terminus ectodomain. The fragment of gp41 protein is linked to an antigen that is not a peptide or protein from HIV, which is presented by HIV VLP. In some aspects, the presented antigen is trimerized. Also disclosed are methods of inducing an immune response against the antigen.

A method of reducing a latent HIV-specific memory-CD4+ T cell pool in a subject includes administering to the subject at least one HIV-1 protein and a pharmaceutically acceptable carrier, wherein the at least one HIV-1 protein is derived from an allogenic infecting HIV-1 virus, and wherein the HIV-1 protein stimulates latent HIV-specific memory CD4+ T cells to induce latent HIV-1 replication resulting in HIV-specific memory-CD4+ T cell death in the subject.

A method of preventing or treating HIV in a subject includes selecting two or more HIV CTL epitopes from an HIV proteome that have a network score that meets a threshold value. The network score for a given epitope can be determined by generating at least one network representing protein structure, calculating a set of network parameters, combining the network parameters to determine a network score for each amino acid residue in the protein structure, generating a network score for each of a plurality of epitopes as a weighted linear combination of the amino acid residues of the epitopes, and selecting two or more epitopes according to their network score. An effective amount of a T cell immunogen composition and a pharmaceutically acceptable carrier is administered to the subject. The T cell immunogen composition includes the two or more selected HIV CTL epitopes.

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 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.

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 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.