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

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

doi:10.5114/bta.2023.132775

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

BioTechnologia (Pozn). 2023 Dec 21;104(4):403-419. doi: 10.5114/bta.2023.132775. eCollection 2023.

Authors

Joanna Baran¹, Łukasz Kuryk², Teresa Szczepińska¹, Michał Łaźniewski¹, Mariangela Garofalo³, Anna Mazurkiewicz-Pisarek¹, Diana Mikiewicz⁴, Alina Mazurkiewicz¹, Maciej Trzaskowski¹, Magdalena Wieczorek², Katarzyna Pancer², Ewelina Hallmann², Lidia Brydak², Dariusz Plewczynski^{5

6}, Tomasz Ciach⁴, Jolanta Mierzejewska⁷, Monika Staniszewska¹

Affiliations

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.

Abstract

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; innate and adaptive immunity; vaccine platform.

Grants and funding

J.B., M.S., M.J., Ł.K., K.P. were supported by BIOTECHMED 1 and BIOTECHMED LAB projects granted by Warsaw University of Technology under the program Excellence Initiative: Research University (IDUB). TS research was cofunded by (POB Biotechnology and Biomedical Engineering) of Warsaw University of Technology within the Excellence Initiative: Research University (IDUB) program. A.M.P., D.M., A.M., T.C., and M.L. were supported by IDUB against the COVID-19 project granted by Warsaw University of Technology under the program Excellence Initiative: Research University (IDUB). DP research was cofunded by the Warsaw University of Technology within the Excellence Initiative: Research University (IDUB) program and cosupported by the Polish National Science Centre (2019/35/O/ST6/02484 and 2020/37/B/NZ2/03757). Computations were performed thanks to the Laboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, using the Artificial Intelligence HPC platform financed by the Polish Ministry of Science and Higher Education (decision no. 7054/IA/SP/2020 of 2020-08-28). Ł.K. was supported by the National Science Centre, Poland, SONATA (2022/47/D/NZ7/03212), SONATINA (2019/32/C/NZ7/00156), and the National Institute of Public Health NIH – National Research Institute, Poland (BW-3/2023, 1BWBW/2022)