September 2023 - Ece Sakalar

Ece Sakalar, MSc

MedUni Wien RESEARCHER OF THE MONTH September 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global COVID-19 pandemic. One possibility to control the pandemic is to induce sterilizing immunity through the induction and maintenance of neutralizing antibodies preventing SARS-CoV-2 from entering human cells to replicate in. A novel SARS-CoV-2 subunit vaccine (PreS-RBD) based on a structurally folded recombinant fusion protein consisting of two SARS-CoV-2 Spike protein receptor binding domains (RBD) fused to the N- and C-terminus of hepatitis B virus (HBV) surface antigen PreS was designed and characterized to enable the two unrelated proteins serving as immunologic carriers for each other. PreS-RBD induced a robust and uniform RBD-specific IgG response, antibodies were detected in serum and mucosal secretions and reacted with SARS-CoV-2 variants, including the omicron variant of concern and the HBV receptor binding sites on PreS of currently known HBV-genotypes. The PreS-RBD vaccine has the potential to serve as a combination vaccine for inducing sterilizing immunity against SARS-CoV-2 and HBV by stopping viral replication through the inhibition of cellular virus entry.

Selected Literature

1. O’Keefe J. and Nadel L. (1978). The hippocampus as a cognitive map. Oxford: Oxford University Press.

2. Fernández-Ruiz, A., Oliva, A., Nagy, G. A., Maurer, A. P., Berényi, A., & Buzsáki, G. (2017). Entorhinal-CA3 dual-input control of spike timing in the hippocampus by theta-gamma coupling. Neuron, 93(5), 1213-1226.

3. Schomburg, E. W., Fernández-Ruiz, A., Mizuseki, K., Berényi, A., Anastassiou, C. A., Koch, C., & Buzsáki, G. (2014). Theta phase segregation of input-specific gamma patterns in entorhinal-hippocampal networks. Neuron, 84(2), 470-485.

4. Lasztóczi, B. and Klausberger, T. (2014). Layer-specific GABAergic control of distinct gamma oscillations in the CA1 hippocampus. Neuron 81.5: 1126-1139.

5. Lasztóczi, B. and Klausberger, T. (2016). Hippocampal place cells couple to three different gamma oscillations during place field traversal. Neuron 91.1: 34-40.

6. Klausberger, T. and Somogyi, P. (2008). Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321.5885: 53-57.

7. Price, C.J., Cauli, B., Kovacs, E.R., Kulik, A., Lambolez, B., Shigemoto, R. and Capogna, M. (2005). Neurogliaform neurons form a novel inhibitory network in the hippocampal CA1 area. Journal of Neuroscience, 25(29), pp.6775-6786.

8. Overstreet-Wadiche, L. and McBain, C.J. (2015). Neurogliaform cells in cortical circuits. Nature Reviews Neuroscience, 16(8), pp.458-468.

9. Sakalar, E., Klausberger, T. and Lasztóczi, B. (2022). Neurogliaform cells dynamically decouple neuronal synchrony between brain areas. Science, 377(6603), pp.324-328.