Academic Journal

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

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
الوصف
تدمد:2076393X
DOI:10.3390/vaccines9030240