Development of innovative and versa tile vector – adjuvant for a designe and production of vaccines against various infectious diseases
In the face of the SARS-COVlD-2 pandemic and no vaccines, our efforts are focused on developing a platform using the non-replicating adenoviruses (AdVs) as universal and highly immunogenic vectors – adjuvants in combination with selected Cov-19’s epitopes (SARS-COVlD-2 etiological agent) for the construction and rapid testing of vaccines against SARS-COVlD-2 (AdCoVAX-2). In the project, AdV serotype 3 or 5 and chimera 5/3 will be used as powerful adjuvants, leading to the recruitment of antigen presenting cells (APC) and the development of cellular and humoral immune responses (against the vector and presented antigens). 1‘3 While infections by the CAR-interacting AdV5 target the airway epithelium, 7 we will use serotype chimerism AdV5/3, for which infection can occur through binding of the desmoglein 2 receptor.3,8-10
Short pentapeptides of S protein subunits (IEDB; www.iedb.org) will be used as epitopes for vaccine production: Sl (id = QHD43416.1) and S2 (id = QHD43419.1).1‘2‘4 We will focus on these promising glycoproteins due to their following properties:l (1) they are foreign to the host immune system; (2) they are highly immunogenic, showing improved safety and efficacy and with lower risk for cross-reactions thus increasing anti-viral specificity; (3) immune response against the spike glycoprotein exert a neutralizing effect; (4) surface glycoprotein is a ligand for human ACE2 in viral entry processes.
Here we will undertake three parts of studies. Part I is to engineer and characterize AdV-replication deficient vector based on serotype 5 or 3 and chimera 5/3. The AdV fiber region responsible for tropism will be appropriately modified to construct the chimera (fiber knob 5/3). AdV5/3 will be created by replacing the AdV5 fiber knob with the AdV3 one, facilitating infection in a DSG2dependent manner.3.8-10 Part Il is to study in vitro pathogenic and replication properties of the patient derived SARS-CoV-19 strains (Staff member employed in NIPH-NIH – Reference National Laboratory conducting diagnostics in SARS-COVlD-19) and pseudo-CoV-19. The COV-19 infection will be studied using 3D Air-Liquid Interface Cultures of human primary airway epithelium (PneumaCultTM-ALl StemCell Technologies). Part Ill is to investigate prophylactic properties of AdCoVAX-2 ex vivo. Immunogenicity will be assessed in preclinical studies using mononuclear cells derived from peripheral blood mononuclear cells (PBMC). We will monitor the maturation of immune cells and the release of proinflammatory cytokines.4S Project is in line with the call announcement as we aim at understanding the mechanisms of the SARS-CoV-2 prevention by development of AdV based vaccine and testing its efficacy in preclinical settings.
As part of the BIOTECHMED-1 Research Grant “Excellence Initiative – Research University” Research Area – Biotechnology and Biomedical Engineering, WUT
Warsaw University of Technology, Centre for Advanced Materials and Technologies CEZAMAT
Department of Virology, National Institute of Public Health, Poland – National Institute of Hygiene
University of Padua, Faculty of Pharmaceutical and Pharmacological Sciences
Jagiellonian University, Faculty of Biochemistry, Biophysics and Biotechnology, Malopolska Centre of Biotechnology
Warsaw University of Technology, Faculty of Chemistry
200 000 pln
Monika Staniszewska PhD, DSc.