Simultaneous CD8+ T-Cell Immune Response against SARS-Cov-2 S, M, and N Induced By Endogenously Engineered Extracellular Vesicles in Both Spleen and Lungs
| العنوان: | Simultaneous CD8+ T-Cell Immune Response against SARS-Cov-2 S, M, and N Induced By Endogenously Engineered Extracellular Vesicles in Both Spleen and Lungs |
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| المؤلفون: | Andrea Giovannelli, Chiara Chiozzini, Flavia Ferrantelli, Patrizia Leone, Francesco Manfredi, Maurizio Federico |
| المصدر: | Vaccines, Vol 9, Iss 240, p 240 (2021) Vaccines Volume 9 Issue 3 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Immunology, lcsh:Medicine, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Immunity, Drug Discovery, CD8+ T cell immunity, Cytotoxic T cell, Pharmacology (medical), Pharmacology, Nef, biology, Chemistry, SARS-CoV-2, lcsh:R, Fusion protein, Cell biology, CTL, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, biology.protein, Antibody, extracellular vesicles, CD8 |
| الوصف: | Most advanced vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 are designed to induce antibodies against spike (S) protein. Differently, we developed an original strategy to induce CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This is a new vaccination approach based on intramuscular injection of DNA expression vectors coding for a biologically inactive HIV-1 Nef protein (Nefmut) with an unusually high efficiency of incorporation into EVs, even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nefmut-fused antigens released by muscle cells can freely circulate into the body and are internalized by antigen-presenting cells. Therefore, EV-associated antigens can be cross-presented to prime antigen-specific CD8+ T-cells. To apply this technology to a strategy of anti-SARS-CoV-2 vaccine, we designed DNA vectors expressing the products of fusion between Nefmut and different viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. We provided evidence that all fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8+ T cell immunity became detectable in spleens and, most important, in lung airways. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lungs. Hence, DNA vectors expressing Nefmut-based fusion proteins can be proposed for new anti-SARS-CoV-2 vaccine strategies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0751b929ae9c89bd3c5f39ea4a3ea394 https://www.mdpi.com/2076-393X/9/3/240 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0751b929ae9c89bd3c5f39ea4a3ea394 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |