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Human Immunodeficiency Virus type 1 (HIV-1) remains a major global health burden, with approximately 38 million people living with HIV worldwide. Although antiretroviral therapy (ART) effectively suppresses viral replication, lifelong treatment is required and viral rebound typically occurs upon interruption.Despite decades of dedicated work, HIV-1 vaccine development has been hindered by genetic hypervariability and immune escape mechanisms, particularly against highly variable proteins such as Env. Targeting more conserved antigens by inducing robust T cell immunity represents a promising strategy for preventive and therapeutic vaccination. In a therapeutic context, T cell-based vaccines may offer an advantage over antibody-driven approaches by targeting infected cells, including those within the replication-competent reservoir. Notably, HIV-1 Gag-specific CD8+ T cell responses have been associated with improved viral control and lower set-point viremia in infected individuals.We developed an innovative T cell vaccine platform based on endogenously engineered extracellular vesicles (EVs). This approach relies on intramuscular injection of DNA vectors expressing a biologically inactive mutant of HIV-1 Nef (Nefmut), which incorporates efficiently into EVs even when fused at its C-terminus with heterologous antigens. EV-associated antigens are taken up by antigen-presenting cells and presented via both MHC class I and II pathways, inducing coordinated antigen-specific CD8+ and CD4+ T cell responses. In preclinical models, this strategy has been already applied successfully against SARS-CoV-2 and tumors (HPV-associated and breast cancer), supporting the robustness and versatility of this platform.To extend this platform to HIV-1, DNA vectors expressing HIV-1 p17, p24, and Tat antigens fused to Nefmut were generated. In vitro assays confirmed expression and efficient EV incorporation of all fusion proteins. In vivo, C57BL/6 mice were then immunized intramuscularly with DNA vectors encoding single or combined Nefmut/antigen constructs, followed by electroporation. Robust antigen-specific T cell responses were detected in splenocytes of immunized mice by IFN-γ ELISpot and intracellular cytokine staining (ICS) upon peptide stimulation. The combined p17/p24/Tat formulation induced stronger cellular responses compared to single-antigen constructs, demonstrating the absence of antigenic interference and supporting the rationale for multi-target T cell strategies that may provide an advantage in limiting viral escape. Overall, this EV-based vaccine platform elicits potent multi-epitope T cell responses against conserved HIV-1 antigens in vivo, highlighting its potential as a versatile strategy for T cell-based HIV-1 vaccination.Ongoing studies in a mouse model of HIV-1 infection based on EcoHIV, a murine-adapted virus mimicking key aspects of HIV-1 infection, will assess functional protective efficacy against infection and correlates of protection.