Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
Allergy - 77(2022), 8 vom: 31. Aug., Seite 2431-2445 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gattinger, Pia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2022 Date Revised 05.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/all.15305 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Gattinger, Pia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 09.08.2022 | ||
| 500 | |a Date Revised 05.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibody response | |
| 650 | 4 | |a neutralizing antibodies | |
| 650 | 4 | |a sterilizing immunity | |
| 650 | 4 | |a vaccine | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Kratzer, Bernhard |e verfasserin |4 aut | |
| 700 | 1 | |a Tulaeva, Inna |e verfasserin |4 aut | |
| 700 | 1 | |a Niespodziana, Katarzyna |e verfasserin |4 aut | |
| 700 | 1 | |a Ohradanova-Repic, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Gebetsberger, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Borochova, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Garner-Spitzer, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Trapin, Doris |e verfasserin |4 aut | |
| 700 | 1 | |a Hofer, Gerhard |e verfasserin |4 aut | |
| 700 | 1 | |a Keller, Walter |e verfasserin |4 aut | |
| 700 | 1 | |a Baumgartner, Isabella |e verfasserin |4 aut | |
| 700 | 1 | |a Tancevski, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Khaitov, Musa |e verfasserin |4 aut | |
| 700 | 1 | |a Karaulov, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Stockinger, Hannes |e verfasserin |4 aut | |
| 700 | 1 | |a Wiedermann, Ursula |e verfasserin |4 aut | |
| 700 | 1 | |a Pickl, Winfried F |e verfasserin |4 aut | |
| 700 | 1 | |a Valenta, Rudolf |e verfasserin |4 aut | |
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