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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to
Pia Gattinger1, Bernhard Kratzer2, Inna Tulaeva1,3
1Department of Pathophysiology and Allergy Research, Division of Immunopathology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Background:
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.
Methods:
We report the construction and in vitro and in vivo characterization of a 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 to enable the two unrelated proteins serving as immunologic carriers for each other.
Results:
PreS-RBD, but not RBD alone, induced a robust and uniform RBD-specific IgG response in rabbits. Currently available genetic SARS-CoV-2 vaccines induce mainly transient IgG1 responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG1 and sustained IgG4 antibody response in a SARS-CoV-2 naive subject. PreS-RBD-specific IgG antibodies were detected in serum and mucosal secretions, 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. PreS-RBD-specific antibodies of the immunized subject more potently inhibited the interaction of RBD with its human receptor ACE2 and their virus-neutralizing titers (VNTs) were higher than median VNTs in a random sample of healthy subjects fully immunized with registered SARS-CoV-2 vaccines or in COVID-19 convalescent subjects.
Conclusion:
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.
Insights
A novel subunit vaccine (PreS-RBD) combining SARS-CoV-2 and HBV antigens elicits robust, sustained neutralizing antibodies against COVID-19 variants. This vaccine shows potential for dual protection against SARS-CoV-2 and hepatitis B virus.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates effective vaccines for sterilizing immunity.
- Neutralizing antibodies are crucial for preventing viral entry and replication.
Purpose of the Study:
- To develop and characterize a novel SARS-CoV-2 subunit vaccine (PreS-RBD).
- To evaluate the immunogenicity and efficacy of PreS-RBD against SARS-CoV-2 and HBV.
Main Methods:
- Constructed a recombinant fusion protein (PreS-RBD) linking SARS-CoV-2 RBD to HBV PreS.
- Assessed vaccine immunogenicity in rabbits and a human subject.
- Evaluated antibody responses, including IgG subclasses, cross-reactivity with variants, and virus-neutralizing activity.
Main Results:
- PreS-RBD induced robust, uniform RBD-specific IgG responses in rabbits.
- The vaccine elicited sustained IgG4 responses alongside IgG1 in a human subject, unlike transient responses from current vaccines.
- PreS-RBD antibodies neutralized SARS-CoV-2 variants, including Omicron, and inhibited RBD-ACE2 interaction more potently than existing vaccines.
Conclusions:
- The PreS-RBD vaccine demonstrates potential for inducing sterilizing immunity against SARS-CoV-2.
- This vaccine may offer a dual protective effect against both SARS-CoV-2 and HBV infections.
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