The present invention is drawn to compositions and methods to enhance an immune response in order to prevent or treat infections or hyperproliferative diseases such as cancer. More particularly, the composition is an immunostimulatory intracellular signaling peptide fused directly or indirectly to a peptide that leads to multimerization into complexes of three or more units, where the intracellular signaling peptide must be present in a complex of three or more units in order to stimulate an immune response. Inserting this fusion construct into viruses like HIV-1 or introducing it into dendritic cells or tumor cells is predicted to lead to a positive therapeutic effect in humans, non-human mammals, birds, and fish.

The present invention concerns in general novel fusion proteins comprising a membrane-transferring moiety and an enzymatic moiety. The present invention further concerns a method of treating disease using said fusion proteins.

The present disclosure provides for recombinant nucleic acids, and cells and virions comprising the recombinant nucleic acids, that can be used to identify, isolate, and/or purify cells latently infected with immunodeficiency virus. A subject recombinant nucleic acid includes (a) a first nucleotide sequence encoding a first reporter polypeptide that produces a first detectable signal, where the first nucleotide sequence is operably linked to an immunodeficiency virus promoter and is translated as an early gene; and (b) a second nucleotide sequence encoding a second reporter polypeptide that produces a second detectable signal that is distinguishable from the first detectable signal, where the second nucleotide sequence is operably linked to a non-immunodeficiency virus promoter. In some aspects, the first and second nucleotide sequences are both positioned between a shared 5 long terminal repeat (LTR) and a shared 3 LTR. Also provided are related methods.

The invention is directed to a system comprising a lentivirus vector particle which encodes at least one guide RNA sequence that is complementary to a first DNA sequence in a host cell genome, a Cas9 protein, and optionally a donor nucleic acid molecule comprising a second DNA sequence. The invention also is directed to a method of altering a DNA sequence in a host cell using such a system, where the host cell can be in a human and the altered DNA can be of the human -globin gene. The invention also is directed to a fusion protein comprising a Cas9 protein and a cyclophilin A (CypA) protein. The invention also is directed to sequences of vectors that can be used in the system and method.

Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

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.

PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

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.

Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

Disclosed herein are compositions comprising a Human Immunodeficiency Virus (HIV) trans-activator of transcription (Tat) derivative polypeptide with increased immunostimulatory properties relative to the native Tat polypeptide, pharmaceutical compositions comprising the Tat derivative polypeptide, and methods of treating cancer using the Tat derivative polypeptide.