Instead of generating immune responses to several HIV proteins and risk over activating more CD4+ T cells (easy targets for HIV-1 infection) as current candidate vaccines try to do, a lower magnitude, narrowly focused, well maintained virus specific CD8+ T cell response to multiple subtypes should destroy and eliminate a few founder viruses without inducing inflammatory responses that may activate more CD4+ T cells and provide more targets for HIV-1 virus infection. Specifically, described herein is a method that focuses the immune response to the 12 protease cleavage sites.

The present disclosure relates to recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.

The present disclosure relates to methods for producing lentiviral vector-producing cells. Specifically the methods utilize two plasmids, rather than four, to provide the required packaging elements and transfer vector to a cell, allowing for the production of a large number of lentiviral producer cells, including suspension-based cells, and the production of high amounts of lentivirus. These methods allow for the production of cells that can be later induced to produce lentivirus, and can be tailored to include a specific gene of interest.

The invention provides methods and compositions for eliciting broad immune responses to HIV envelope proteins. The methods include use of nucleic acids constructs that encode conserved elements of HIV Env to induce immune responses.

Human cytomegalovirus vectors comprising heterologous antigens are disclosed. The vectors derived from the TR strain, are ganciclovir-sensitive, include active US2, US3, US6, US7 and UL131A genes, and have a deleterious or inactivating mutation in the UL82 gene preventing the expression of pp71.

This disclosure relates to the field of research and clinical usage of extracellular vesicles. More in particular, this disclosure relates to usages of recombinant extracellular vesicles comprising a) a self-assembling protein that directs its own release through vesicles as a luminal membrane-bound protein and b) a heterologous marker. Indeed, the disclosure provides recombinant extracellular vesicles that can be used as a biological reference material in methods to quantify extracellular vesicles in a sample, and/or, that can be used to calibrate a device for sample extracellular vesicles analysis, and/or, that can be used to evaluate the isolation process of extracellular vesicles. This disclosure thus relates to improving the accuracy of an extracellular vesicle-based diagnosis.

The present disclosure relates to methods for producing lentiviral vector-producing cells. Specifically the methods utilize two plasmids, rather than four, to provide the required packaging elements and transfer vector to a cell, allowing for the production of a large number of lentiviral producer cells, including suspension-based cells, and the production of high amounts of lentivirus. These methods allow for the production of cells that can be later induced to produce lentivirus, and can be tailored to include a specific gene of interest.

A virus-like particle encapsulating a target protein is provided. The virus-like particle contain a Gag protein, and the Gag protein forms a dimer with the target protein.

Instead of generating immune responses to several HIV proteins and risk over activating more CD4+ T cells (easy targets for HIV-1 infection) as current candidate vaccines try to do, a lower magnitude, narrowly focused, well maintained virus specific CD8+ T cell response to multiple subtypes should destroy and eliminate a few founder viruses without inducing inflammatory responses that may activate more CD4+ T cells and provide more targets for HIV-1 virus infection. Specifically, described herein is a method that focuses the immune response to the 12 protease cleavage sites.

Disclosed herein are mosaic conserved region HIV polypeptides and immunogenic polypeptides including one or more of the mosaic conserved region polypeptides. In some embodiments, the immunogenic polypeptides are included in an immunogenic composition, such as a polyvalent immunogenic composition. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more of the disclosed immunogenic polypeptides or compositions to a subject having or at risk of HIV infection. In some embodiments, the methods include inducing an immune response in a subject comprising administering to the subject at least one of the disclosed immunogenic polypeptides or a nucleic acid encoding at least one of the immunogenic polypeptides.