Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model

Pia Gattinger; Bernhard Kratzer; Al Nasar Ahmed Sehgal; Anna Ohradanova-Repic; Laura Gebetsberger; Gabor Tajti; Margarete Focke-Tejkl; Mirjam Schaar; Verena Fuhrmann; Lukas Petrowitsch; Walter Keller; Sandra Högler; Hannes Stockinger; Winfried F Pickl; Rudolf Valenta

doi:10.3390/vaccines12030229

Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model

Vaccines (Basel). 2024 Feb 23;12(3):229. doi: 10.3390/vaccines12030229.

Authors

Pia Gattinger¹, Bernhard Kratzer², Al Nasar Ahmed Sehgal², Anna Ohradanova-Repic³, Laura Gebetsberger³, Gabor Tajti³, Margarete Focke-Tejkl^{1

4}, Mirjam Schaar¹, Verena Fuhrmann¹, Lukas Petrowitsch⁵, Walter Keller⁵, Sandra Högler⁶, Hannes Stockinger³, Winfried F Pickl², Rudolf Valenta^{1

4

7

8}

Affiliations

¹ Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria.
² Institute of Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria.
³ Institute for Hygiene and Applied Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria.
⁴ Karl Landsteiner University of Health Sciences, 3500 Krems, Austria.
⁵ Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, 8010 Graz, Austria.
⁶ Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
⁷ Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
⁸ NRC Institute of Immunology FMBA of Russia, 115478 Moscow, Russia.

Abstract

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants have dominated in the spread of the disease. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently, we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs.

Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies.

Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro using protein chemical methods, mass spectrometry, and circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum-hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study the specific antibody and cytokine responses, safety and Omicron neutralization.

Results: Defined and pure immunogens could be produced in significant quantities as secreted and folded proteins in mammalian cells. The antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, the RBD-specific IgG levels induced with the different vaccines were comparable, but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were seven- and twofold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively, and they were six-fold higher than those of the bivalent vaccine.

Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Keywords: COVID-19; Omicron; SARS-CoV-2; neutralizing antibodies; vaccine.

Abstract

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