tetano
Editor, Senior Moderator
Allergy
. 2022 Mar 31.
doi: 10.1111/all.15305. Online ahead of print.
Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
Pia Gattinger[SUP] 1 [/SUP], Bernhard Kratzer[SUP] 2 [/SUP], Inna Tulaeva[SUP] 1 3 [/SUP], Katarzyna Niespodziana[SUP] 1 4 [/SUP], Anna Ohradanova-Repic[SUP] 5 [/SUP], Laura Gebetsberger[SUP] 5 [/SUP], Kristina Borochova[SUP] 1 [/SUP], Erika Garner-Spitzer[SUP] 6 [/SUP], Doris Trapin[SUP] 2 [/SUP], Gerhard Hofer[SUP] 7 [/SUP], Walter Keller[SUP] 8 [/SUP], Isabella Baumgartner[SUP] 9 [/SUP], Ivan Tancevski[SUP] 10 [/SUP], Musa Khaitov[SUP] 11 12 [/SUP], Alexander Karaulov[SUP] 3 [/SUP], Hannes Stockinger[SUP] 5 [/SUP], Ursula Wiedermann[SUP] 6 [/SUP], Winfried F Pickl[SUP] 2 4 [/SUP], Rudolf Valenta[SUP] 1 3 4 [/SUP]
Affiliations
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 IgG[SUB]1[/SUB] responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG[SUB]1[/SUB] and sustained IgG[SUB]4[/SUB] antibody response in a SARS-CoV-2 naïve 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 health 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.
. 2022 Mar 31.
doi: 10.1111/all.15305. Online ahead of print.
Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants
Pia Gattinger[SUP] 1 [/SUP], Bernhard Kratzer[SUP] 2 [/SUP], Inna Tulaeva[SUP] 1 3 [/SUP], Katarzyna Niespodziana[SUP] 1 4 [/SUP], Anna Ohradanova-Repic[SUP] 5 [/SUP], Laura Gebetsberger[SUP] 5 [/SUP], Kristina Borochova[SUP] 1 [/SUP], Erika Garner-Spitzer[SUP] 6 [/SUP], Doris Trapin[SUP] 2 [/SUP], Gerhard Hofer[SUP] 7 [/SUP], Walter Keller[SUP] 8 [/SUP], Isabella Baumgartner[SUP] 9 [/SUP], Ivan Tancevski[SUP] 10 [/SUP], Musa Khaitov[SUP] 11 12 [/SUP], Alexander Karaulov[SUP] 3 [/SUP], Hannes Stockinger[SUP] 5 [/SUP], Ursula Wiedermann[SUP] 6 [/SUP], Winfried F Pickl[SUP] 2 4 [/SUP], Rudolf Valenta[SUP] 1 3 4 [/SUP]
Affiliations
- PMID: 35357709
- DOI: 10.1111/all.15305
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 IgG[SUB]1[/SUB] responses in vaccinated subjects whereas the PreS-RBD vaccine induced RBD-specific IgG antibodies consisting of an early IgG[SUB]1[/SUB] and sustained IgG[SUB]4[/SUB] antibody response in a SARS-CoV-2 naïve 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 health 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.