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The C-Terminal Domain of Nef(mut) Is Dispensable for the CD8(+) T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles
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 thr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068889/ https://www.ncbi.nlm.nih.gov/pubmed/33921215 http://dx.doi.org/10.3390/vaccines9040373 |
Sumario: | 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. |
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