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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1452814
This article is part of the Research Topic SARS-CoV-2 Vaccines Beyond the Pandemic Era View all 15 articles

Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O) combining RBDs from Wuhan hu-1 wild type and Omicron BA.1

Provisionally accepted
Pia Gattinger Pia Gattinger 1Liubov I Kozlovskaya Liubov I Kozlovskaya 2Alexander S. Lunin Alexander S. Lunin 2Olga Gancharova Olga Gancharova 2Dina I. Sirazova Dina I. Sirazova 2Vasiliy D. Apolokhov Vasiliy D. Apolokhov 2Egor S. Chekina Egor S. Chekina 2Ilya Gordeychuk Ilya Gordeychuk 2Alexander Victor Karaulov Alexander Victor Karaulov 3Rudolf Valenta Rudolf Valenta 1*Aydar A. Ishmukhametov Aydar A. Ishmukhametov 2
  • 1 Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
  • 2 Chumakov Federal Scientific Center for Research and Development of Immune-and- Biological Products (RAS), Moscow, Moscow Oblast, Russia
  • 3 Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia

The final, formatted version of the article will be published soon.

    In this perspective 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 fusion protein-based vaccine approach 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 anti-body (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 titres from the lungs were measured using a plaque-forming assay. We found that W-PreS-Ovaccinated hamsters developed robust nABs against Omicron BA.1, showed almost no development of pneumonia, and had significantly reduced infectious virus titres 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-ofconcept 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.

    Keywords: SARS-CoV-2, COVID-19, omicron, Vaccine, fusion protein-based vaccine, neutralizing antibodies, Infection model, Syrian hamster

    Received: 21 Jun 2024; Accepted: 03 Jan 2025.

    Copyright: © 2025 Gattinger, Kozlovskaya, Lunin, Gancharova, Sirazova, Apolokhov, Chekina, Gordeychuk, Karaulov, Valenta and Ishmukhametov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rudolf Valenta, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, A-1090, Austria

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.