The present invention is directed to antigen binding proteins including, but not limited to, monoclonal antibodies and antigen binding fragments thereof, that specifically bind to and preferably neutralize human cytomegalovirus (CMV). The antigen binding proteins of the invention are useful as a prophylactic and/or therapeutic agent for preventing and/or treating CMV infections in a patient in need thereof. Also encompassed by the invention are pharmaceutical compositions comprising the antigen binding proteins of the invention and a pharmaceutically acceptable carrier. The invention further relates to methods of using the antigen binding proteins and pharmaceutical compositions of the invention for the prevention or treatment of CMV infection in patients in need thereof.

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.

The invention provides improved non-human vertebrates and non-vertebrate cells capable of expressing antibodies comprising human variable region sequences. The present invention is directed to the provision of long HCDR3s from non-human vertebrates and cells. The present invention is also directed to the provision of novel V, D and J pairings in immunoglobulin heavy and light chain loci. Novel, biased antibody diversities and potentially expanded diversities are provided. The invention also provides for novel and potentially expanded diversity or diversity that is biased towards variable gene usage common to antibodies useful for treating and/or preventing certain diseases or conditions, such as infectious diseases. The invention also provides methods of generating antibodies using such vertebrates, as well as the antibodies per se, therapeutic compositions thereof and uses.

Provided herein are compositions comprising recombinant mammalian cells that express recombinant T cell rectors with specificity against EBV or CMV peptide:MHC antigens. Also provided are therapeutic methods of using the recombinant mammalian cells as cell therapies against viral infections.

Particular aspects provide for use of the β-herpesvirus Cytomegalovirus (CMV: e.g., RhCMV and HCMV) as a uniquely evolved “vector” for safely initiating and indefinitely maintaining high level cellular and humoral immune responses (against, e.g., HIV, SIV, TB, etc.). Particular aspects provide a method for treatment or prevention of, e.g., HIV, SIV or TB, comprising infection of a subject in need thereof with at least one recombinant CMV-based vector (e.g., HCMV or RhCMV) comprising an expressible HIV/SIV/TB antigen or a variant or fusion protein thereof. In particular embodiments of the method, infection is of an immunocompetent, HCMV or RhCMV seropositive subject. Additional aspects provide for RhCMV- and HCMV-based vaccine vectors, and versions thereof with suicide or safety means. Further aspects provide pharmaceutical compositions comprising the inventive CMV-based vaccine vectors.

Provided herein are methods of treating or preventing human cytomegalovirus (HCMV) infection comprising modulating interactions between the HCMV gHgLgO trimer and plasma membrane-expressed host cell proteins, as well as methods of identifying modulators of such interactions.

An object of the present invention is to provide a means for rapidly diagnosing infection with VZV. The present invention relates to an antibody against VZVgE or an antibody fragment thereof, and an immunological measurement method and an immunological measurement device using the antibody or the antibody fragment thereof, etc.

Particular aspects provide for use of the β-herpesvirus Cytomegalovirus (CMV: e.g., RhCMV and HCMV) as a uniquely evolved “vector” for safely initiating and indefinitely maintaining high level cellular and humoral immune responses (against, e.g., HIV, SIV, TB, etc.). Particular aspects provide a method for treatment or prevention of, e.g., HIV, SIV or TB, comprising infection of a subject in need thereof with at least one recombinant CMV-based vector (e.g., HCMV or RhCMV) comprising an expressible HIV/SIV/TB antigen or a variant or fusion protein thereof. In particular embodiments of the method, infection is of an to immunocompetent, HCMV or RhCMV seropositive subject. Additional aspects provide for RhCMV- and HCMV-based vaccine vectors, and versions thereof with suicide or safety means. Further aspects provide pharmaceutical compositions comprising the inventive CMV-based vaccine vectors.

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

The present invention relates to Shiga toxin effector polypeptides with reduced antigenic and/or immunogenic potential. Immunogenicity can be a limitation for the repeated administration to mammals of proteins and polypeptides derived from Shiga toxins. The Shiga toxin effector polypeptides of the present invention have uses as components of therapeutics, diagnostics, and immunization materials. The cytotoxic proteins of the present invention have uses for selective killing of specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, immune disorders, and microbial infections. The proteins of the present invention also have uses for detecting specific cell types, collecting diagnostic information, and monitoring the treatment of a variety of diseases, such as, e.g., cancers, immune disorders, and microbial infections.