The invention relates to a novel class of antagonistic and inverse agonistic anti-US28 antibodies, more specifically to single heavy chain variable domain antibodies (VHH) and variants and modifications thereof. The invention further relates to methods for producing these antibodies and to the use of the antibodies in methods for diagnostic and therapeutic purposes, especially for treatment of an individual suffering from a CMV-positive tumor such as glioblastoma.

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeting molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell-targeting molecules of the present invention may be used for the targeted killing of specific cell types and the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeting molecules of the invention exhibit improved, in vivo tolerability as compared to related cell-targeting molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeting molecules of the invention can deliver additional materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, into the interiors of target cells.

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeting molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell-targeting molecules of the present invention may be used for the targeted killing of specific cell types and the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeting molecules of the invention exhibit improved, in vivo tolerability as compared to related cell-targeted molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeting molecules of the invention can deliver additional materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, into the interiors of target cells.

Vaccines are provided that elicit neutralizing antibodies to Epstein-Barr virus (EBV). Some vaccines comprise nanoparticles that display envelope proteins from EBV on their surface. The nanoparticles comprise fusion proteins comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to at least a portion of an EBV envelope protein. The fusion proteins self-assemble to form the envelope protein-displaying nanoparticles. Such vaccines can be used to vaccinate an individual against infection by different types of Epstein-Barr viruses as well as Epstein-Barr viruses that are antigenically divergent from the virus from which the EBV envelope protein was obtained. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.

Disclosed are vaccine compositions comprising a VLP comprising two or more EBV envelope glycoproteins and one or more T cell antigens and methods of preventing or treating EBV infections using the vaccine compositions. Also disclosed is an expression system or a single expression vector for co-expressing two or more EBV envelope glycoproteins simultaneously to generate a VLP vaccine. The expression system may include a single vector inserted with two or more nucleic acid sequences that encode two or more EBV envelope glycoproteins linked by one or more linking sequences such that the EBV envelope glycoproteins are co-expressed simultaneously.

A recombinant, humanized antibody or antibody fragment that is capable of at least partly preventing or inhibiting Epstein Barr Virus gp350 binding to a human cell. The antibody may be useful for passively immunizing humans against Epstein Barr Virus and/or treating or preventing Epstein Barr Virus-associated diseases, disorders or conditions. The antibody or antibody fragment may also be used to detect Epstein Barr Virus.

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

The present invention relates to the treatment of HCMV relates diseases. The inventors conducted a study to find an essential domain of pUL56 for its interaction with pUL89 which is important in the effect of the CMV. Sequences alignments allowed them to predict one sequence in C-terminal of pUL56 potentially necessary for interaction with pUL89. BAC mutagenesis and AlphaLISA technologies using purified proteins allowed to validate that the short sequence .sub.671WMVVKYMGFF.sub.680 (SEQ ID NO: 1) in C-terminal of pUL56 is involved in interaction with pUL89. Knowing this important information, antibodies directed against this sequence or peptides derived from this sequence could be useful to invalidate the interaction of pUL56 to pUL89 and thus to treat HCMV related diseases. Thus, the present invention relates to an isolated anti-pUL56 antibody, binding to the SEQ ID NO:1 or a peptide comprising the amino acids sequence: WMVVKYMGFF (SEQ ID NO: 1) or a function-conservative variant thereof for use in the treatment of HCMV related diseases.

Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Epstein Barr Virus infection in mammals, and to methods of using those compositions of matter for the same. Also disclosed are proteins, referred to as anti-gp350 antibody probes, and anti-gp350 B-cell probes, that maintain the epitope structure of the CR2-binding region of gp350, but do not bind CR2.

Anti-Epstein Barr Virus (EBV) antibodies and vaccines are described herein. The antibodies and vaccines can be used to treat and/or reduce the risk of EBV infection and to treat and/or reduce the risk of complications associated with EBV infection, such as infectious mononucleosis, lymphoproliferative disorders, carcinomas, and smooth muscle tumors.