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.

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.

Provided are methods of detecting replication competent virus, e.g., replication competent retrovirus such as gammaretrovirus or lentivirus, in a sample containing a cell transduced with a viral vector particle encoding a recombinant and or heterologous molecule, e.g., heterologous gene product. The methods may include assessing transcription of one or more target genes, such as viral genes, that are expressed in a retrovirus but not expressed in the viral vector particle. Replication competent retrovirus may be determined to be present if the levels of RNA of the one or more target genes is higher than a reference value, which can be measured directly or indirectly, including from a positive control sample containing RNA from the respective target gene at a known level and/or at or above the limit of detection of the assay.

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.

Disclosed herein are methods and compositions for treating a subject having or at risk of having an HIV infection. Disclosed herein are peptide immunogens and nucleic acids that have epitopes in which mutations are most likely to have deleterious effects on the HIV virus. An algorithm is disclosed for the selection of the epitopes based on the HIV fitness landscape, and it accounts for the effect of coupling mutations.

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.

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.

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.

The invention relates to retroviral producer cell comprising nucleic acid sequences encoding: gag and pol proteins; envelope protein or a functional substitute thereof; amplifiable selection marker; and the RNA genome of the retroviral vector particle, wherein said nucleic acid sequences are all integrated at a single locus within the retroviral producer cell genome. The invention also relates to nucleic acid vectors comprising a non-mammalian origin of replication and the ability to hold at least 25 kilobases (kb) of DNA, characterized in that said nucleic acid vector comprises retroviral nucleic acid sequences encoding: gag and pol proteins, and an env protein or a functional substitute thereof. The nucleic acid vector additionally comprises nucleic acid sequences encoding an amplifiable selection marker. The invention also relates to uses and methods using said nucleic acid vector in order to produce stable retroviral packaging and producer cell lines.

The present invention pertains to the field of T Cell receptors (TCR) identification and clonotyping, and especially concerns particular TCRs identified by clonotyping of a HIV-specific TCR repertoire, or fragments thereof. The invention relates especially to TCRs recognizing Gag peptide located between positions 293-312 in the GAG protein of HIV-1. The present invention further relates to nucleic acid constructs suitable as means for cloning or expressing nucleic acid molecules or TCRs of the invention, such as plasmids, vectors, especially lentiviraltransfer vectors. The invention is of particular interest in the context of therapeutic treatment of human beings seropositive for HIV.