The present disclosure relates to recombinant HIV Env polypeptides and their use in the treatment and prevention of HIV/AIDS.

Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

The present invention relates to engineered cells expressing a fusion protein comprising a peptide fusion inhibitor and a CXCR4 protein that lacks signaling activity. Also provided are methods of suppressing, inhibiting, preventing or treating a HIV infection in a subject in need thereof using the engineered cells.

The invention is directed to mosaic HIV-1 envelopes, and methods of using the same to induce ADCC responses.

The invention relates to retroviral producer cell comprising nucleic acid sequences encoding: gag and pol proteins; envelope protein or a functional substitute thereof; amplifiable selection marker; and the RNA genome of the retroviral vector particle, wherein said nucleic acid sequences are all integrated at a single locus within the retroviral producer cell genome. The invention also relates to nucleic acid vectors comprising a non-mammalian origin of replication and the ability to hold at least 25 kilobases (kb) of DNA, characterized in that said nucleic acid vector comprises retroviral nucleic acid sequences encoding: gag and pol proteins, and an env protein or a functional substitute thereof. The nucleic acid vector additionally comprises nucleic acid sequences encoding an amplifiable selection marker. The invention also relates to uses and methods using said nucleic acid vector in order to produce stable retroviral packaging and producer cell lines.

The present disclosure relates to methods for generating broadly neutralizing bovine anti-HIV Env antibodies, compositions comprising the broadly neutralizing bovine antibodies, and methods of treatment or prevention of HIV using the broadly neutralizing bovine antibodies. In certain embodiments, a broadly neutralizing bovine antibody comprises a polyclonal F(ab) or F(ab′)2 fragment. In certain embodiments, a broadly neutralizing bovine antibody comprises a humanized bovine monoclonal antibody.

Human immunodeficiency virus (HIV) envelope proteins having mutations that stabilize the trimeric form of the envelope protein are provided. The HIV envelope proteins have certain amino acid substitutions at specified positions in the envelope protein sequence. The HIV envelope proteins described herein have an improved percentage of trimer formation and/or an improved trimer yield as compared to an HIV envelope protein that does not have one or more of the indicated amino acid substitutions. Also provided are nucleic acid molecules and vectors encoding the HIV envelope proteins, as well as compositions containing the HIV envelope proteins, nucleic acid, and vectors.

The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Human immunodeficiency virus (HIV) envelope proteins having mutations that stabilize the trimeric form of the envelope protein are provided. The HIV envelope proteins have certain amino acid substitutions at specified positions in the envelope protein sequence. The HIV envelope proteins described herein have an improved percentage of trimer formation and/or an improved trimer yield as compared to an HIV envelope protein that does not have one or more of the indicated amino acid substitutions. Also provided are nucleic acid molecules and vectors encoding the HIV envelope proteins, as well as compositions containing the HIV envelope proteins, nucleic acid, and vectors.

Compositions containing a nucleic acid nanostructure having a desired geometric shape and antigens bound to its surface are provided. The nanostructures can be, for example, in the form of a 6-helix bundle or icosahedron. The nanostructure design allows for control of the relative position and/or stoichiometry of the antigen bound to its surface. The antigens displayed on the nanostructure surface are arranged with the preferred number, spacing, and 3D organization to elicit a robust immune response. The displayed antigen can be an HIV immunogen such as eOD-GT6, eOD-GT8, or variants thereof. The compositions may thus be useful as immunogens, vaccines, immunostimulators, adjuvants, and the like. Methods of inducing immune responses, inducing protective immunity, inducing the production of neutralizing antibodies or inhibitory antibodies, inducing tolerance, and treating cancer, infectious or autoimmune diseases are also provided.