التفاصيل البيبلوغرافية
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 |
المؤلفون: |
Flavia Ferrantelli, Chiara Chiozzini, Francesco Manfredi, Andrea Giovannelli, Patrizia Leone, Maurizio Federico |
المصدر: |
Vaccines, Vol 9, Iss 3, p 240 (2021) |
بيانات النشر: |
MDPI AG, 2021. |
سنة النشر: |
2021 |
المجموعة: |
LCC:Medicine |
مصطلحات موضوعية: |
SARS-CoV-2, extracellular vesicles, CD8+ T cell immunity, Nef, Medicine |
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. |
نوع الوثيقة: |
article |
وصف الملف: |
electronic resource |
اللغة: |
English |
تدمد: |
2076-393X |
Relation: |
https://www.mdpi.com/2076-393X/9/3/240; https://doaj.org/toc/2076-393X |
DOI: |
10.3390/vaccines9030240 |
URL الوصول: |
https://doaj.org/article/72125878bdb04ff2b5ec0ad58334154f |
رقم الانضمام: |
edsdoj.72125878bdb04ff2b5ec0ad58334154f |
قاعدة البيانات: |
Directory of Open Access Journals |