Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants

Pia Gattinger; Bernhard Kratzer; Inna Tulaeva; Katarzyna Niespodziana; Anna Ohradanova-Repic; Laura Gebetsberger; Kristina Borochova; Erika Garner-Spitzer; Doris Trapin; Gerhard Hofer; Walter Keller; Isabella Baumgartner; Ivan Tancevski; Musa Khaitov; Alexander Karaulov; Hannes Stockinger; Ursula Wiedermann; Winfried F Pickl; Rudolf Valenta

doi:10.1111/all.15305

Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants

Allergy. 2022 Aug;77(8):2431-2445. doi: 10.1111/all.15305. Epub 2022 Apr 15.

Authors

Pia Gattinger¹, Bernhard Kratzer², Inna Tulaeva^{1

3}, Katarzyna Niespodziana^{1

4}, Anna Ohradanova-Repic⁵, Laura Gebetsberger⁵, Kristina Borochova¹, Erika Garner-Spitzer⁶, Doris Trapin², Gerhard Hofer⁷, Walter Keller⁸, Isabella Baumgartner⁹, Ivan Tancevski¹⁰, Musa Khaitov^{11

12}, Alexander Karaulov³, Hannes Stockinger⁵, Ursula Wiedermann⁶, Winfried F Pickl^{2

4}, Rudolf Valenta^{1

3

4

11}

Affiliations

¹ Department of Pathophysiology and Allergy Research, Division of Immunopathology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
² Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
³ Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia.
⁴ Karl Landsteiner University of Health Sciences, Krems, Austria.
⁵ Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, Austria.
⁶ Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
⁷ Department of Materials and Environmental Chemistry, University of Stockholm, Stockholm, Sweden.
⁸ Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, Graz, Austria.
⁹ Department of Ophthalmology, Medical University Vienna, Vienna, Austria.
¹⁰ Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
¹¹ NRC Institute of Immunology FMBA of Russia, Moscow, Russia.
¹² Pirogov Russian National Research Medical University, Moscow, Russia.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; antibody response; neutralizing antibodies; sterilizing immunity; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines* / immunology
COVID-19* / prevention & control
Humans
Immunoglobulin G
Pandemics / prevention & control
Rabbits
SARS-CoV-2*
Spike Glycoprotein, Coronavirus* / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants