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.

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.

Publication date: Feb 23, 2024

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

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Concepts Keywords
Antibodies COVID-19
Capable neutralizing antibodies
Coronavirus Omicron
Hydroxide SARS-CoV-2
vaccine

Semantics

Type Source Name
disease VO vaccine
disease VO Hepatitis B virus
disease MESH COVID-19
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH endemic disease
disease VO SARS-CoV-2 protein
disease VO immunized
drug DRUGBANK Aluminium
drug DRUGBANK Hydroxide ion
drug DRUGBANK Aluminum hydroxide
disease VO vaccination
disease VO dose
disease VO subunit vaccine
disease VO vaccine candidate
disease MESH Hepatitis
disease MESH Allergy
drug DRUGBANK Coenzyme M
disease MESH chronic illnesses
disease IDO host
disease MESH infection
disease VO passive immunization
disease VO effectiveness
disease VO population
disease VO vaccine antigen
disease VO immunization
drug DRUGBANK Sodium lauryl sulfate
disease IDO cell
disease VO time
disease VO USA
disease IDO blood
disease VO volume

Original Article

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