Academic Journal

The C-Terminal Domain of Nefmut Is Dispensable for the CD8+ T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles

التفاصيل البيبلوغرافية
العنوان: The C-Terminal Domain of Nefmut Is Dispensable for the CD8+ T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles
المؤلفون: Chiara Chiozzini, Francesco Manfredi, Flavia Ferrantelli, Patrizia Leone, Andrea Giovannelli, Eleonora Olivetta, Maurizio Federico
المصدر: Vaccines, Vol 9, Iss 4, p 373 (2021)
بيانات النشر: MDPI AG, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
مصطلحات موضوعية: extracellular vesicles, HIV-1 Nef, DNA immunization, CD8+ T cell immunity, HPV vaccines, SARS-CoV-2 vaccines, Medicine
الوصف: Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nefmut 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 Nefmut-derivatives released by muscle cells. In the perspective of a possible translation into the clinic of the Nefmut-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nefmut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nefmut 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 Nefmut 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 Nefmut truncation does not influence stability, EV-anchoring, and CD8+ T cell immunogenicity of the fused antigen. Hence, the C-terminal deleted Nefmut may represent a safer alternative to the full-length isoform for vaccines in humans.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2076-393X
Relation: https://www.mdpi.com/2076-393X/9/4/373; https://doaj.org/toc/2076-393X
DOI: 10.3390/vaccines9040373
URL الوصول: https://doaj.org/article/863f59beec024b64840311d45176b793
رقم الانضمام: edsdoj.863f59beec024b64840311d45176b793
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2076393X
DOI:10.3390/vaccines9040373