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Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
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Number of Authors: 192022 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 77, no 8, p. 2431-2445Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2022. Vol. 77, no 8, p. 2431-2445
Keywords [en]
antibody response, COVID-19, neutralizing antibodies, SARS-CoV-2, sterilizing immunity, vaccine
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-204370DOI: 10.1111/all.15305ISI: 000782709200001PubMedID: 35357709Scopus ID: 2-s2.0-85128174685OAI: oai:DiVA.org:su-204370DiVA, id: diva2:1656085
Available from: 2022-05-04 Created: 2022-05-04 Last updated: 2024-06-04Bibliographically approved

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Hofer, Gerhard

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Department of Materials and Environmental Chemistry (MMK)
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