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BioTechnologia
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4/2023
vol. 104
 
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abstract:
RESEARCH PAPERS

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

Joanna Baran
1
,
Łukasz Kuryk
2
,
Teresa Szczepińska
1
,
Michał Łaźniewski
1
,
Mariangela Garofalo
3
,
Anna Mazurkiewicz-Pisarek
1
,
Diana Mikiewicz
4
,
Alina Mazurkiewicz
1
,
Maciej Trzaskowski
1
,
Magdalena Wieczorek
2
,
Katarzyna Pancer
2
,
Ewelina Hallmann
2
,
Lidia Brydak
2
,
Dariusz Plewczynski
5, 6
,
Tomasz Ciach
4
,
Jolanta Mierzejewska
7
,
Monika Staniszewska
1

  1. Centre for Advanced Materials and Technologies, Warsaw University of Technology, Warsaw, Poland
  2. National Institute of Public Health, Warsaw, Poland
  3. University of Padova, Padova, Italy
  4. Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland
  5. Faculty of Mathematics and Information Science, Warsaw University of Technology, Warsaw, Poland
  6. Centre of New Technologies, University of Warsaw, Warsaw, Poland
  7. Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland
BioTechnologia vol. 104(4) ∙ pp. 403–419 ∙ 2023
DOI: https://doi.org/10.5114/bta.2023.132775
Online publish date: 2023/12/21
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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.
keywords:

adenoviral vectors; vaccine platform; innate and adaptive immunity


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