TY - JOUR
T1 - Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
AU - Gattinger, Pia
AU - Kratzer, Bernhard
AU - Tulaeva, Inna
AU - Niespodziana, Katarzyna
AU - Ohradanova-Repic, Anna
AU - Gebetsberger, Laura
AU - Borochova, Kristina
AU - Garner-Spitzer, Erika
AU - Trapin, Doris
AU - Hofer, Gerhard
AU - Keller, Walter
AU - Baumgartner, Isabella
AU - Tancevski, Ivan
AU - Khaitov, Musa
AU - Karaulov, Alexander
AU - Stockinger, Hannes
AU - Wiedermann, Ursula
AU - Pickl, Winfried F
AU - Valenta, Rudolf
N1 - Funding Information:
Rudolf Valenta has received research grants from HVD Life‐Sciences, Vienna, Austria, WORG Pharmaceuticals, Hangzhou, China and from Viravaxx AG, Vienna, Austria. He serves as consultant for Viravaxx AG. Rudolf Valenta, Pia Gattinger, Bernhard Kratzer, and Winfried Pickl are authors on a patent application regarding the vaccine. The other authors have no conflict of interest to declare.
Funding Information:
This study was supported by grants from Austrian Science Fund, Grant numbers: DK‐W1248 and P29398; Viravaxx AG; and Danube Allergy Research Cluster of Lower Austria, Grant number: 330950005. AOR and HS also acknowledge funding by the Austrian Science Fund (FWF, grant number P34253‐B). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Animals
KW - Antibodies, Neutralizing
KW - Antibodies, Viral
KW - COVID-19 Vaccines/immunology
KW - COVID-19/prevention & control
KW - Humans
KW - Immunoglobulin G
KW - Pandemics/prevention & control
KW - Rabbits
KW - SARS-CoV-2
KW - Spike Glycoprotein, Coronavirus/immunology
UR - http://www.scopus.com/inward/record.url?scp=85128174685&partnerID=8YFLogxK
U2 - 10.1111/all.15305
DO - 10.1111/all.15305
M3 - Journal article
C2 - 35357709
SN - 0105-4538
VL - 77
SP - 2431
EP - 2445
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 8
ER -