In vitro immune evaluation of adenoviral vector-based platform for infectious diseases

Autor: Joanna Baran, Łukasz Kuryk, Teresa Szczepińska, Michał Łaźniewski, Mariangela Garofalo, Anna Mazurkiewicz-Pisarek, Diana Mikiewicz, Alina Mazurkiewicz, Maciej Trzaskowski, Magdalena Wieczorek, Katarzyna Pancer, Ewelina Hallmann, Lidia Brydak, Dariusz Plewczynski, Tomasz Ciach, Jolanta Mierzejewska, Monika Staniszewska
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: BioTechnologia, Vol 104, Iss 4, Pp 403-419 (2023)
Druh dokumentu: article
ISSN: 0860-7796
2353-9461
DOI: 10.5114/bta.2023.132775
Popis: New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2±0.7% vs. 23.1±2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0±1.3% vs. 36.0±3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1±0.8% vs. 82.3±0.4%) or rRBD (94.6±0.3% vs. 82.3±0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness.
Databáze: Directory of Open Access Journals
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