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Strong SARS-CoV-2 N-Specific CD8+ T Immunity Induced by Engineered Extracellular Vesicles Associates with Protection from Lethal Infection in Mice

1
National Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
2
National Center for Animal Experimentation and Welfare, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
3
Core Facilities, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Célia F. Rodrigues
Viruses 2022, 14(2), 329; https://doi.org/10.3390/v14020329
Received: 12 January 2022 / Revised: 3 February 2022 / Accepted: 4 February 2022 / Published: 6 February 2022
(This article belongs to the Topic Infectious Diseases)
SARS-CoV-2-specific CD8+ T cell immunity is expected to counteract viral variants in both efficient and durable ways. We recently described a way to induce a potent SARS-CoV-2 CD8+ T immune response through the generation of engineered extracellular vesicles (EVs) emerging from muscle cells. This method relies on intramuscular injection of DNA vectors expressing different SARS-CoV-2 antigens fused at their N-terminus with the Nefmut protein, i.e., a very efficient EV-anchoring protein. However, quality, tissue distribution, and efficacy of these SARS-CoV-2-specific CD8+ T cells remained uninvestigated. To fill the gaps, antigen-specific CD8+ T lymphocytes induced by the immunization through the Nefmut-based method were characterized in terms of their polyfunctionality and localization at lung airways, i.e., the primary targets of SARS-CoV-2 infection. We found that injection of vectors expressing Nefmut/S1 and Nefmut/N generated polyfunctional CD8+ T lymphocytes in both spleens and bronchoalveolar lavage fluids (BALFs). When immunized mice were infected with 4.4 lethal doses of 50% of SARS-CoV-2, all S1-immunized mice succumbed, whereas those developing the highest percentages of N-specific CD8+ T lymphocytes resisted the lethal challenge. We also provide evidence that the N-specific immunization coupled with the development of antigen-specific CD8+ T-resident memory cells in lungs, supporting the idea that the Nefmut-based immunization can confer a long-lasting, lung-specific immune memory. In view of the limitations of current anti-SARS-CoV-2 vaccines in terms of antibody waning and efficiency against variants, our CD8+ T cell-based platform could be considered for a new combination prophylactic strategy. View Full-Text
Keywords: SARS-CoV-2; vaccines; CD8+ T cell immunity; extracellular vesicles; Nef SARS-CoV-2; vaccines; CD8+ T cell immunity; extracellular vesicles; Nef
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MDPI and ACS Style

Ferrantelli, F.; Chiozzini, C.; Manfredi, F.; Leone, P.; Spada, M.; Di Virgilio, A.; Giovannelli, A.; Sanchez, M.; Cara, A.; Michelini, Z.; Federico, M. Strong SARS-CoV-2 N-Specific CD8+ T Immunity Induced by Engineered Extracellular Vesicles Associates with Protection from Lethal Infection in Mice. Viruses 2022, 14, 329. https://doi.org/10.3390/v14020329

AMA Style

Ferrantelli F, Chiozzini C, Manfredi F, Leone P, Spada M, Di Virgilio A, Giovannelli A, Sanchez M, Cara A, Michelini Z, Federico M. Strong SARS-CoV-2 N-Specific CD8+ T Immunity Induced by Engineered Extracellular Vesicles Associates with Protection from Lethal Infection in Mice. Viruses. 2022; 14(2):329. https://doi.org/10.3390/v14020329

Chicago/Turabian Style

Ferrantelli, Flavia, Chiara Chiozzini, Francesco Manfredi, Patrizia Leone, Massimo Spada, Antonio Di Virgilio, Andrea Giovannelli, Massimo Sanchez, Andrea Cara, Zuleika Michelini, and Maurizio Federico. 2022. "Strong SARS-CoV-2 N-Specific CD8+ T Immunity Induced by Engineered Extracellular Vesicles Associates with Protection from Lethal Infection in Mice" Viruses 14, no. 2: 329. https://doi.org/10.3390/v14020329

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