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.

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.

Compositions and methods of use are provided to boost a primed immune response to HIV. More specifically, the present invention relates to vaccine compositions comprising an HIV-protein boost or an MVA-expressed Env protein and methods of use. Exemplary HIV proteins for protein boosts include proteins such as gp120 proteins B.63521A11mutC and full-length single chain (FLSC), which has been modified to stabilize a CD4-induced Env structure. Exemplary MVAs expressing secreted Methods of administration and dosing regimens are also provided.

Disclosed are compositions for generating an immune response against human immunodeficiency virus (HIV) and their methods of uses.

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.

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 subject invention pertains to materials and methods for detecting, preventing and treating retroviral infections in humans and other animals susceptible to infection by retrovirus. It has been discovered that FIV can be transmitted from cats to humans and that the FIV can infect human cells in vivo and that antibodies generated by the infected person cross-react with HIV antigens. Thus, the methods and compositions of the subject invention can be used to detect, prevent and treat FIV infection in humans and other non-feline animals that are susceptible to FIV infection. The methods and compositions of the invention can also be used to prevent and treat infection by HIV in humans.

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.

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.