Zobrazeno 1 - 6 of 6 pro vyhledávání: '"Ghenassia, Alexandre"'
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Dissertation/ Thesis
Induction de réponses mémoires lymphocytaires T CD8 et protection vaccinale après transfert de gènes par le vecteur AAV recombinant
Autor: Ghenassia, Alexandre
La mémoire immunologique est le mécanisme biologique fondamental à la base du développement de la vaccination. La compréhension de ce mécanisme ainsi que de ses interactions avec les différents acteurs du système immunitaire a permis l’éla
Externí odkaz: http://www.theses.fr/2015USPCB028/document
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A key aspect to consider for vaccinal protection is the induction of a local line of defense consisting of nonrecirculating tissue-resident memory T cells (TRM), in parallel to the generation of systemic memory CD8+ T cell responses. The potential to induce TRM has now been demonstrated for a number of pathogens and viral vectors. This potential, however, has never been tested for recombinant adeno-associated virus (rAAV) vectors, which are weakly inflammatory and poor transducer of dendritic cells. Using a model rAAV2/1-based vaccine, we determined that a single intradermal immunization with rAAV2/1 vectors in mice induces fully functional TRM at the local site of immunization. The optimal differentiation of rAAV-induced transgene-specific skin TRM was dependent on local transgene expression and additional CD4+ T cell help. Transgene expression in dendritic cells, however, appeared to be dispensable for the priming of transgene-specific skin TRM, suggesting that this process solely depends on the cross-presentation of transgene products. Overall, this study provides needed information to properly assess rAAV vectors as T cell-inducing vaccine carriers.IMPORTANCE rAAVs display numerous characteristics that could make them extremely attractive as vaccine carriers, including an excellent safety profile in humans and great flexibility regarding serotypes and choice of target tissue. Studies addressing the ability of rAAV to induce protective T cell responses, however, are scarce. Notably, the potential to induce a tissue-resident memory T cell response has never been described for rAAV vectors, strongly limiting further interest for their use as vaccine carriers. Using a model rAAV2/1 vaccine delivered to the skin, our study demonstrated that rAAV vectors can induce bona fide skin resident TRM and provides additional clues regarding the cellular mechanisms underlying this process. These results will help widen the field of rAAV applications
Autor: Gross, David-Alexandre, Ghenassia, Alexandre, Bartolo, Laurent, Urbain, Dominique, Benkhelifa-Ziyyat, Sofia, Lorain, Stéphanie, Davoust, Jean, Chappert, Pascal
Publikováno v: Journal of Virology
Journal of Virology, American Society for Microbiology, 2019, 93 (5), ⟨10.1128/JVI.01334-18⟩
International audience
Externí odkaz: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::433f68e20305b1877ca66fa92b834b0d
https://hal.archives-ouvertes.fr/hal-02392833
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Akademický článek
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Plný text Recenzováno Digitální knihovna AV ČR
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