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
Affiliations
Pia Gattinger
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Bernhard Kratzer
Institute of Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Al Nasar Ahmed Sehgal
Institute of Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Anna Ohradanova-Repic
Institute for Hygiene and Applied Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Laura Gebetsberger
Institute for Hygiene and Applied Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Gabor Tajti
Institute for Hygiene and Applied Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Margarete Focke-Tejkl
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Mirjam Schaar
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Verena Fuhrmann
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Lukas Petrowitsch
Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, 8010 Graz, Austria
Walter Keller
Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, 8010 Graz, Austria
Sandra Högler
Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
Hannes Stockinger
Institute for Hygiene and Applied Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Winfried F. Pickl
Institute of Immunology, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
Rudolf Valenta
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Infectiology and Immunology, Center for Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria
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.