Compositions and methods to increase the in vivo capacity of CD8+ T cells to kill HIV-infected and reactivated latent HIV-infected T cells (LHITC) to functionally cure HIV infection or improve the clinical course. Compositions and methods to increase the in vivo capacity of CD8+ T cells to kill CMV or CMV-infected cells are also provided.

An expression system for expressing a herpesvirus glycoprotein complex including a vector inserted with two or more nucleic acid sequences that encode two or more subunits of a herpesvirus glycoprotein complex linked by one or more linking sequences such that the subunits are co-expressed simultaneously and self-processed to assemble into a glycoprotein complex. The expression system or the vector can be included in a vaccine composition. The vaccine composition can be used for preventing or treating herpesvirus infections.

Disclosed herein are compositions and uses thereof for detecting HIV latency reversal, isolating cells with HIV latency reversal, treating HIV infection, and/or reversing latency in HIV infected CD4+ T cells. In some aspects, disclosed herein is a composition and uses thereof for treating HIV infection, wherein the composition comprises one or more mature monocyte-derived dendritic cells (MDGs) having an HIV peptide bound to a Class I major histocompatibility complex (MHC) molecule and a herpesvirus peptide bound to one or more Class II MHC molecules.

The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided.

An isolated human cytomegalovirus (HCMV) membrane protein complex that comprises gH, gL and at least one more HCMV glycoprotein is provided. In some embodiments the complex consists of gH, gL and gO. In other embodiments the complex consists of gH, gL, pUL128, pUL130 and pUL131A. Processes for expressing and purifying such complexes, and subsequent uses of such complexes in immunogenic compositions and vaccines, are also provided.

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

A long-chain peptide antigen includes a plurality of epitopes. An interepitope sequence located between two of the plurality of epitopes contains four to ten consecutive tyrosines, threonines, alanines, histidines, glutamines, or asparagines. The killer T-cell recognition epitopes form complexes with MHC class I molecules and are recognized by CD8+ killer T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The helper T-cell recognition epitopes form complexes with MHC class II molecules and are recognized by CD4+ helper T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The peptide is cleaved within the first interepitope sequence upon uptake of the peptide into antigen-presenting cells. The long-chain peptide antigen may be administered to a patient together with a hydrophobized polysaccharide, such as cholesterol-modified pullulan, and/or an adjuvant, such as CpG oligo DNA.

The present invention relates to a peptide-MHC-I-antibody fusion protein for use as a therapeutic medicament administered to a patient, wherein a cellular cytotoxic immune response towards the virus-derived peptide has been amplified in the patient. The therapeutic medicament may be used in a kit of parts and administered in combination with an amplifying medicament and optionally an inducing medicament. The inducing medicament and the amplifying medicament may be for use in a method of making a patient susceptible for a treatment with the peptide-MHC-I-antibody fusion protein. The medicament(s) may be used for the treatment of diseases, such as cancer or a viral infection.

The technology described herein relates to modified T cells and their use in immunotherapeutic methods. In various examples, the T cells are modified so as to decrease or eliminate CD3ζ, TRAC, and/or TRBC expression.

The present invention relates to the field of immunotherapy, in particular, to adoptive T cell therapy, T cell receptor (TCR) gene therapy and vaccination. The invention provides a method for preparing a nucleic acid encoding the TCR alpha chain construct (TRA) and TCR beta chain construct (TRB) of a TCR construct specific for an epitope from an antigen presented on major histocompatibility complex (MHC), comprising contacting T cells isolated from a donor with a library of artificial antigen presenting cells (APC) comprising cells expressing all MHC I or MHC II alleles present in the donor, preferably, in K562 cells. The TCR construct can be expressed in a T cell, which is useful for adoptive T cell therapy, e.g., of cancer, viral infections or autoimmune diseases. The invention further provides a method for identifying the epitope recognized by said TCR. Immunogenic epitopes recognized by said TCRs can be used to develop vaccine formulations to induce antigen-specific T cell immunity in patients. The invention further provides pairs of two TCR constructs and respective immunogenic epitopes obtained by the method of the invention, wherein the epitopes are from human papillomavirus (HPV) 16 (also designated alphapapillomavirus 9) oncoprotein E5 and human cytomegalovirus (CMV) protein pp65.