July 2023 - Pia Gattinger

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Dr. Pia Gattinger

MedUni Wien RESEARCHER OF THE MONTH July 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. Gattinger, P., Kratzer, B., Tulaeva, I., Niespodziana, K., Ohradanova-Repic, A., Gebetsberger, L., Borochova, K. Garner-Spitzer, E., Trapin, D., Hofer, G., Keller, W., Baumgartner, I., Tancevski, I., Khaitov, M., Karaulov, A., Stockinger, H., Wiedermann, U., Pickl, W.F. & Valenta, R. Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants. Allergy. 2022. 77(8):2431-2445 doi:10.1111/all.15305

2. Gattinger, P., Borochova, K., Dorofeeva, Y., Henning, R., Kiss, R., Kratzer, B., Mühl, B., Perkmann, T., Trapin, D., Trella, M., Ettel, P., Tulaeva, I., Pickl, W.F. & Valenta R. Antibodies in serum of convalescent patients following mild COVID-19 do not always prevent virus-receptor binding. Allergy. 2021. 76(3):878-883. doi: 10.1111/all.14523.

3. Gattinger, P., Niespodziana, K., Stiasny K., Sahanic, S., Tulaeva, I., Borochova, K., Dorofeeva, Y.,  Schlederer, T., Sonnweber, T., Hofer, G., Kiss, R.,  Kratzer, K., Trapin, D., Tauber, PA., Rottal, A., Körmöczi, U., Feichter, M., Weber, M., Focke-Tejkl, M., Löffler-Ragg, J., Mühl, B., Kropfmüller, A., Keller, W., Stolz, F., Henning, R., Tancevski, I., Puchhammer-Stöckl, E., Pickl, W.F. & Valenta, R.  Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes. Allergy. 2022. 77(1):230-242. doi: 10.1111/all.15066.

4. Gattinger P., Tulaeva, I., Borochova, K., Kratzer, B., Trapin, D., Kropfmüller, A., Pickl, W.F. & Valenta R. Omicron: A SARS-CoV-2 variant of real concern. Allergy. 2022. 77(5):1616-1620. doi: 10.1111/all.15264

5. Mair, M.J., Mitterer, M., Gattinger, P., Berger, J.M., Valenta, R., Fong, D. & Preusser, M. Inhibition of SARS-CoV-2 Omicron BA.1 and BA.4 after fourth vaccination or tixagevimab/cilgavimab in cancer patients. JAMA Oncology. 2022. 8(11):1694-1696. doi:10.1001/jamaoncol.2022.4226.

6. Mair, M.J., Mitterer, M., Gattinger, P., Berger, J.M., Trutschnig, W., Bathke, A.C., Gansterer, M., Berghoff, A.S., Laengle, S. Gottmann, L., Buratti, T., Haslacher, H., Lamm, W.W., Raderer, M., Tobudic, S., Fuereder, T., Valenta, R., Fong, D. & Preusser, M. SARS-CoV-2 breakthrough infections in patients with cancer. Cancer Cell. 2022. 40(5), 444–446. doi: 10.1016/j.ccell.2022.04.003

7. Palmrich, P., Roessler, B., Wisgrill, L., Kampf, S., Gattinger, P., Valenta, R., Fleischmann, E., Berger, A., Kiss, H. & Farr, A. Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19. BMC Pregnancy Childbirth. 2021 Aug 26;21(1):587. doi: 10.1186/s12884-021-04059-y.

8. Kopanja, S.*, Gattinger P.*, Schmidthaler, K.,  Sieber, J.,  Niepodziana, K., Schlederer, Weseslindtner, L., Stiasny, K., Götzinger, F., Pickl, W.F., Frischer, T., Valenta, R., & Szépfalusi, Z. Characterization of the antibody response to SARS-CoV-2 in a mildly affected paediatric population. Pediatr Allergy Immunol. 2022. 33(2), e13737. doi: 10.1111/pai.13737. *contributed equally

9. Agerer, B., Koblischke, M., Gudipati, V., Montaño-Gutierrez, L.F., Smyth, M., Popa, A., Genger, J.W., Endler, L., Florian, D.M., Mühlgrabner, V., Graninger. M., Aberle, S.W., Husa, A.M., Shaw, L.E., Lercher, A., Gattinger, P., Torralba-Gombau, R., Trapin, D., Penz, T., Barreca, D., Fae, I., Wenda, S., Traugott, M., Walder, G., Pickl, W.F., Thiel, V., Allerberger, F., Stockinger, H., Puchhammer-Stöckl, E., Weninger, W., Fischer, G., Hoepler, W., Pawelka, E., Zoufaly, A., Valenta, R., Bock, C., Paster, W., Geyeregger, R., Farlik, M., Halbritter, F., Huppa, J.B., Aberle, J.H. & Bergthaler, A. SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8+ T cell responses. Sci Immunol. 2021. 4;6(57):eabg6461. doi: 10.1126/sciimmunol.abg6461.

10. Kratzer, B., Trapin, D., Ettel, P., Körmöczi, U., Rottal, A., Tuppy, F., Feichter, M., Gattinger, P., Borochova, K., Dorofeeva, Y., Tulaeva, I., Weber, M., Grabmeier-Pfistershammer, K., Tauber, P. A., Gerdov, M., Mühl, B., Perkmann, T., Fae, I., Wenda, S., Führer, H., Henning, R., Valenta, R. & Pickl, W. F. Immunological imprint of COVID-19 on human peripheral blood leukocyte populations. Allergy, 2020. 76(3), 751–765.  doi:10.1111/all.14647

11. Kratzer, B., Schlax, L.C., Gattinger, P., Waidhofer-Söllner, P., Trapin, D., Tauber, P.A., Sehgal, A.N.A., Körmöczi, U., Rottal, A., Feichter, M., Oberhofer, T., Grabmeier-Pfistershammer, K., Borochova, K., Dorofeeva, Y., Tulaeva, I., Weber, M., Mühl, B., Kropfmüller, A., Negrin, B., Kundi, M., Valenta, R. & Pickl, W.F. Combined assessment of S- and N-specific IL-2 and IL-13 secretion and CD69 neo-expression for discrimination of post-infection and post-vaccination cellular SARS-CoV-2-specific immune response. Allergy. 2022. 77(11):3408-3425. doi: 10.1111/all.15406.