Abstract: Methods and compositions are provided which employ chimeric polypeptides having at least one heterologous epitope for a human immunodeficiency virus type 1 (HIV-1) neutralizing antibody. These chimeric polypeptides behave as molecular scaffolds which are capable of presenting the various heterologous HIV-1 epitopes. The invention demonstrates that a heterologous epitope recognized by the HIV-1 neutralizing antibody can be more fully exposed to neutralizing antibodies when presented within the backbone of the chimeric polypeptide than when the epitope is presented within the context of an HIV-1 backbone. Polynucleotides encoding these chimeric polypeptides are also provided. Immunogenic compositions are provided which comprise a chimeric polypeptide having at least one heterologous epitope that interacts with an HIV-1 neutralizing antibody. Immuno genie compositions comprising chimeric polynucleotides encoding the chimeric polypeptides of the invention are also provided.

Abstract: The present disclosure relates to stabilized forms of the HIV gp120 envelope protein in complex with the broadly neutralizing CD4-binding site antibody b12, to crystalline forms of the stabilized forms of the HIV gp120 envelope protein in complex with the broadly neutralizing CD4-binding site antibody b12, and to the high resolution structure obtained from these crystals by X-ray diffraction methods. Methods for identifying immunogenic polypeptides based on these structures are also disclosed.

Abstract: The present application is directed to stabilized HIV envelope glycoprotein trimers. The trimers are stabilized by introducing trimeric motifs, preferably the GCN4 coiled coil or the fibritin trimeric domain, at certain sites, for example in the gp41 ectodomain. These stabilized trimers or DNA molecules encoding such trimers can be used to generate an immunogenic reaction. The trimers can also be used in assays to screen for molecules that interact with them—and to identify molecules that interact with specific sites.

Abstract: This invention provides methods, kits and automated systems for identifying a reagent in which a compound crystallizes, and methods for crystallizing a compound.

Abstract: A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has cysteine amino acid residues introduced to create disulfide bonds, a cavity is filled with hydrophobic amino acids, a Proresidue is introduced at a defined turn structure of the protein, or the hydrophobicity is increased across the interface between different domains, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has more than one of those characteristics. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp120.

Abstract: The present application is directed to stabilized HIV envelope glycoprotein trimers. The trimers are stabilized by introducing trimeric motifs, preferably the GCN4 coiled coil or the fibritin trimeric domain at certain sites, for example in the gp41 ectodomain. These stabilized trimers or DNA molecules encoding such trimers can be used to generate an immunogenic reaction. The trimers can also be used in assays to screen for molecules that interact with them—and to identify molecules that interact with specific sites.

Abstract: A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has at least two of the glycosylation sites proximal to the CD4 binding site or chemokine receptor site altered so that the alteration prevents glycosylation at that site or where glycosylation sites distal to these sites have been derivatized with a molecular adjuvant, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has both changes. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp 120.

Abstract: This invention provides a non-naturally occurring targeted lipolytic compound comprising a lipolytic agent linked to a targeting agent. In an embodiment, the lipolytic agent is covalently attached to the targeting agent. In an embodiment, the lipolytic agent is a phospholipase and the targeting agent is a viral receptor. This invention further provides for therapeutic uses of the non-naturally occurring targeted lipolytic compound. In an embodiment, the non-naturally occurring targeted lipolytic compound neutralizes virions of the human immunodeficiency virus (HIV).

Abstract: This invention provides a non-naturally occurring targeted lipolytic compound comprising a lipolytic agent linked to a targeting agent. In an embodiment, the lipolytic agent is covalently attached to the targeting agent. In an embodiment, the lipolytic agent is a phospholipase and the targeting agent is a viral receptor. This invention further provides for therapeutic uses of the non-naturally occurring targeted lipolytic compound. In an embodiment, the non-naturally occurring targeted lipolytic compound neutralizes virions of the human immunodeficiency virus (HIV).