Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)

In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated...

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Main Authors: Pia Gattinger, Luibov I. Kozlovskaya, Alexander S. Lunin, Olga S. Gancharova, Dina I. Sirazova, Vasiliy D. Apolokhov, Egor S. Chekina, Ilya V. Gordeychuk, Alexander V. Karaulov, Rudolf Valenta, Aydar A. Ishmukhametov
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1452814/full
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author Pia Gattinger
Luibov I. Kozlovskaya
Alexander S. Lunin
Olga S. Gancharova
Dina I. Sirazova
Dina I. Sirazova
Vasiliy D. Apolokhov
Egor S. Chekina
Ilya V. Gordeychuk
Ilya V. Gordeychuk
Alexander V. Karaulov
Alexander V. Karaulov
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Aydar A. Ishmukhametov
Aydar A. Ishmukhametov
author_facet Pia Gattinger
Luibov I. Kozlovskaya
Alexander S. Lunin
Olga S. Gancharova
Dina I. Sirazova
Dina I. Sirazova
Vasiliy D. Apolokhov
Egor S. Chekina
Ilya V. Gordeychuk
Ilya V. Gordeychuk
Alexander V. Karaulov
Alexander V. Karaulov
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Aydar A. Ishmukhametov
Aydar A. Ishmukhametov
author_sort Pia Gattinger
collection DOAJ
description In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These fusion proteins are made to increase the immunogenicity of the vaccine antigens and/or to enable special targeting of the immune system. The protein-based vaccine approach is exemplified solely in a proof of concept study by using W-PreS-O, a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 with the hepatitis B virus (HBV)-derived PreS surface antigen adsorbed to aluminum hydroxide. The W-PreS-O vaccine was evaluated in Syrian hamsters which were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo) before they were infected with Omicron BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. We found that W-PreS-O-vaccinated hamsters developed robust nABs against Omicron BA.1, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. The data of our proof-of-concept study provides compelling evidence that the W-PreS-O vaccine has protective effect against Omicron BA.1 in a Syrian hamster in vivo infection model and thus support the promising results obtained also for other fusion protein-based SARS-CoV-2 vaccines.
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spelling doaj-art-19f97e82bf1b4c8f80037f8b2a9e48912025-01-28T11:25:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14528141452814Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)Pia Gattinger0Luibov I. Kozlovskaya1Alexander S. Lunin2Olga S. Gancharova3Dina I. Sirazova4Dina I. Sirazova5Vasiliy D. Apolokhov6Egor S. Chekina7Ilya V. Gordeychuk8Ilya V. Gordeychuk9Alexander V. Karaulov10Alexander V. Karaulov11Rudolf Valenta12Rudolf Valenta13Rudolf Valenta14Rudolf Valenta15Aydar A. Ishmukhametov16Aydar A. Ishmukhametov17Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Division of Immunopathology, Medical University of Vienna, Vienna, AustriaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaInstitute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaInstitute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, RussiaLaboratory for Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, RussiaLife Improvement by Future Technologies (LIFT) Center, Moscow, RussiaCenter for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Division of Immunopathology, Medical University of Vienna, Vienna, AustriaLaboratory for Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, RussiaLife Improvement by Future Technologies (LIFT) Center, Moscow, RussiaCenter for Molecular Allergology, Karl Landsteiner University of Health Sciences, Krems, AustriaChumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, RussiaInstitute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, RussiaIn this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These fusion proteins are made to increase the immunogenicity of the vaccine antigens and/or to enable special targeting of the immune system. The protein-based vaccine approach is exemplified solely in a proof of concept study by using W-PreS-O, a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 with the hepatitis B virus (HBV)-derived PreS surface antigen adsorbed to aluminum hydroxide. The W-PreS-O vaccine was evaluated in Syrian hamsters which were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo) before they were infected with Omicron BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. We found that W-PreS-O-vaccinated hamsters developed robust nABs against Omicron BA.1, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. The data of our proof-of-concept study provides compelling evidence that the W-PreS-O vaccine has protective effect against Omicron BA.1 in a Syrian hamster in vivo infection model and thus support the promising results obtained also for other fusion protein-based SARS-CoV-2 vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1452814/fullSARS-CoV-2COVID-19omicronvaccinefusion protein-based vaccineneutralizing antibodies
spellingShingle Pia Gattinger
Luibov I. Kozlovskaya
Alexander S. Lunin
Olga S. Gancharova
Dina I. Sirazova
Dina I. Sirazova
Vasiliy D. Apolokhov
Egor S. Chekina
Ilya V. Gordeychuk
Ilya V. Gordeychuk
Alexander V. Karaulov
Alexander V. Karaulov
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Rudolf Valenta
Aydar A. Ishmukhametov
Aydar A. Ishmukhametov
Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
Frontiers in Immunology
SARS-CoV-2
COVID-19
omicron
vaccine
fusion protein-based vaccine
neutralizing antibodies
title Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
title_full Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
title_fullStr Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
title_full_unstemmed Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
title_short Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)
title_sort fusion protein based covid 19 vaccines exemplified by a chimeric vaccine based on a single fusion protein w pres o
topic SARS-CoV-2
COVID-19
omicron
vaccine
fusion protein-based vaccine
neutralizing antibodies
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1452814/full
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