The present invention relates, in general, to human immunodeficiency virus (HIV), and, in particular, to a method of inducing neutralizing antibodies to HIV and to compounds and compositions suitable for use in such a method.

This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.

Disclosed herein are compounds (such as peptides or peptide mimetics) that bind to HIV RRE RNA. In some examples, the compounds inhibit (for example, decrease) binding of Rev to the RRE RNA. In some embodiments, the compounds include two moieties, each of which bind to one of the Rev binding sites in the RRE. In some examples, the moieties include peptides or small molecules. In some examples, the peptides include an arginine-rich motif. The RRE binding compounds may be further linked to a detectable label or cargo moiety. Also disclosed are methods of treating or inhibiting HIV including administering one or more of the disclosed compounds to a subject.

Provided are engineered cells (such as stem cells or T cells) that have a surface molecule comprising a membrane-tethered binding moiety that binds to a T cell surface antigen (such as CCR5, CD4 or CXCR4) or a HIV antigen, or a membrane tethered inhibitory moiety that inhibits the membrane fusion of HIV (such as C34). Also provided are methods of making and using these engineered cells.

A method for determining HIV-1 co-receptor tropism in an HIV-infected patient includes preparing an HIV-1 envelope protein coding sequence from a sample, introducing the HIV-1 envelope protein coding sequence into a first expression construct using yeast homologous recombination, and using the first expression construct in a cell to cell fusion assay to determine HIV-1 co-receptor tropism.

Compounds (such as peptides or peptide mimetics) that bind to HIV RRE RNA are provided. In some examples, the compounds inhibit (for example, decrease) binding of Rev to the RRE RNA. In some embodiments, the compounds include two moieties, each of which bind to one of the Rev binding sites in the RRE. In some examples, the moieties include peptides or small molecules. In some examples, the peptides include an arginine-rich motif. The RRE binding compounds may be further linked to a detectable label or cargo moiety. Also provided are methods of treating or inhibiting HIV including administering one or more of the RRE binding compounds to a subject.

The invention provides improved gene therapy methods and compositions.

The present invention generally relates to compositions and methods for inducing an adaptive immune response in a subject. In certain embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof. For example, in certain embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof.

The invention relates to novel non-human transgenic animals, which upon antigenic stimulation are capable of producing monovalent antibodies binding to a selected antigen, modified heavy chain transgenes, methods for producing the non-human transgenic animals, methods for immunizing the non-human transgenic animals for as well as monovalent antibodies obtainable by such immunization methods.

Described herein are dose escalation regimens for the administration of complexes comprising interleukin-15 (IL-15) covalently or noncovalently bound to IL-15 receptor alpha (IL-15R) to patients in order to enhance IL-15-mediated immune function. In a specific aspect, the dose escalation regimens are useful in the prevention, treatment, and/or management of disorders in which enhancing IL-15-mediated function is beneficial, such as cancer, infectious diseases, immunodeficiencies and lymphopenia. In another specific aspect, the dose escalation regimens are useful for eradicating or reducing HIV in HIV-infected patients.