Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nef mut fused at its C-terminus to viral and tumor antigens elicit a potent, effective, and anti-tolerogenic CD8 + T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nef mut -derivatives released by muscle cells. In the perspective of a possible translation into the clinic of the Nef mut -based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nef mut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nef mut to associate with EVs. The EV-anchoring function was also preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. Most important, the Nef mut C-terminal deletion did not affect levels, quality, and diffusion at distal sites of the antigen-specific CD8 + T immunity. We concluded that the C-terminal Nef mut truncation does not influence stability, EV-anchoring, and CD8 + T cell immunogenicity of the fused antigen. Hence, the C-terminal deleted Nef mut may represent a safer alternative to the full-length isoform for vaccines in humans.
【저자키워드】 Extracellular vesicles, SARS-CoV-2 vaccines, CD8+ T cell immunity, HIV-1 Nef, DNA immunization, HPV vaccines, 【초록키워드】 SARS-CoV-2, Vaccine, immune response, Immunity, translation, CD8, Antigen, Protein, DNA, T cell, stability, cells, humans, vector, vaccine platform, safety profile, Heterologous, Perspective, injection, C-terminus, full-length, diffusion, MOST, isoform, EVs, Vesicle, effective, Extracellular, S1 and S2, elicit, not affect, expressing, deleted, released, C-terminal, fused, distal, preserved, tumor antigen, 【제목키워드】 immunogenicity, CD8,