The present invention relates to the manufacture of a diverse repertoire of functional heavy chain-only antibodies that undergo affinity maturation, and uses thereof. The invention also relates to the manufacture and use of a diverse repertoire of class-specific heavy chain-only antibodies and to the manufacture and use of multivalent polypeptide complexes with antibody heavy chain functionality, preferably antibody heavy chain binding functionality, constant region effector activity and, optionally, additional effector functions.

The present invention also relates to a method of generation of fully functional heavy chain-only antibodies in transgenic mice in response to antigen challenge. In particular, the present invention relates to a method for the generation of human antigen-specific, high affinity, heavy chain-only antibodies of any class, or mixture of classes and the isolation and expression of fully functional VH antigen-binding domains.

The subject invention concerns methods and materials for inducing an immune response in an animal or person against an immunodeficiency virus, such as HIV, SIV, or FIV. In one embodiment, a method of the invention comprises administering one or more antigens and/or immunogens to the person or animal wherein the antigen and/or immunogen comprises one or more evolutionarily conserved epitopes of immunodeficiency viruses. In one embodiment, the epitope is one that is conserved between HIV and SIV, or between HIV and FIV. In another embodiment, the epitope is one that is conserved between HIV, SIV, and FIV.

System for detecting an antigen comprising: a first fusion protein with no luciferase activity comprising: a N-terminal domain which comprises a first single domain antibody which is directed against a first epitope of said antigen and a C-terminal domain which comprises a first fragment of a luciferase having the amino acid sequence SEQ ID NO: 1 or is a variant thereof and a second fusion protein with no luciferase activity comprising: a N-terminal domain which comprises a second single domain antibody which is directed against a second epitope of said antigen and a C-terminal domain which comprises a second fragment of a luciferase having the amino acid sequence SEQ ID NO: 2 or is a variant thereof. Luminescence is emitted in the presence of a substrate when both the first fusion protein and the second fusion protein bind to said antigen.

The subject invention concerns methods and materials for inducing an immune response in an animal or person against an immunodeficiency virus, such as HIV, SIV, or FIV. In one embodiment, a method of the invention comprises administering one or more antigens and/or immunogens to the person or animal wherein the antigen and/or immunogen comprises one or more evolutionarily conserved epitopes of immunodeficiency viruses. In one embodiment, the epitope is one that is conserved between HIV and SIV, or between HIV and FIV. In another embodiment, the epitope is one that is conserved between HIV, SIV, and FIV.

A method for detecting HIV infection in a mammal is disclosed. The method contains the steps of isolating exosomes from a urine sample of a mammal and detecting the presence of HIV-specific biomarker in said isolated exosomes. A method for diagnosing a mammal with an HIV-associated disease, in particular, HIV-associated nephropathy is also disclosed.

The present application generally relates to methods of genetically modifying a T-cell comprising a chimeric antigen receptor wherein the T-cell lacks a co-receptor for HIV. The application further relates to methods of making a nucleic acid encoding a chimeric antigen receptor, nucleic acids encoding a chimeric antigen receptor, and genetically modified T-cells comprising a chimeric antigen receptor disclosed herein. The application further relates to methods of treating, inhibiting, or ameliorating HIV in a subject including administering to the subject a cell disclosed herein.

A method for detecting HIV infection in a mammal is disclosed. The method contains the steps of isolating exosomes from a urine sample of a mammal and detecting the presence of HIV-specific biomarker in said isolated exosomes. A method for diagnosing a mammal with an HIV-associated disease, in particular, HIV-associated nephropathy is also disclosed.

Methods to inhibit the formation of retrovirus integrase reaching dimers, to dissociate retrovirus integrase reaching dimers, and to stabilize retrovirus integrase reaching dimers in a conformation in which retrovirus DNA-to host cell DNA integration activity of the integrase is inhibited are provided. Methods for treating a retrovirus infection, which target retrovirus integrase reaching dimer formation and/or stability are also provided.

Provided herein, in some aspects, are binding molecules including co-binders having high affinity and/or high specificity to a target. In other aspects, provided herein are compositions, methods of making, and methods of using the binding molecules taught herein, such as diagnostic and therapeutic methods of use involving the co-binders taught herein