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Development and Preclinical Evaluation of Virus Like Particle Vaccine Against COVID-19 Infection
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  • Ismail Yilmaz C,
  • Emre Ipekoglu,
  • Artun Bulbul,
  • Nilsu Turay,
  • Muzaffer Yildirim,
  • Irem Evcili,
  • Naz Yilmaz,
  • Yagmur Aydin,
  • Bilgi Gungor,
  • Nese Guvencli,
  • Berfu Saraydar,
  • Asli Gulce Bartan,
  • Bilgehan Ibibik,
  • Tugce Bildik,
  • İlayda Baydemir,
  • Hatice Asena Sanli,
  • Basak Kayaoglu,
  • Yasemin Ceylan,
  • Tugce Yildirim,
  • Irem Abras,
  • Ihsan Cihan Ayanoglu,
  • Sefa Burak Cam,
  • Eda Ciftci Dede,
  • Merve Gizer,
  • Osman Erganis,
  • Fahriye Sarac,
  • Serdar Uzar,
  • Hakan Enul,
  • Cumhur Adiay,
  • Gamze Aykut,
  • Hivda Polat,
  • Ismail Selim Yildirim,
  • Saban Tekin,
  • Hasan E. Zeytin,
  • Petek Korkusuz,
  • Ihsan Gursel,
  • Mayda Gursel
Ismail Yilmaz C
Middle East Technical University Department of Biological Sciences Ankara Turkey

Corresponding Author:[email protected]

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Emre Ipekoglu
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Artun Bulbul
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Nilsu Turay
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Muzaffer Yildirim
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Irem Evcili
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Naz Yilmaz
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Yagmur Aydin
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Bilgi Gungor
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Nese Guvencli
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Berfu Saraydar
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Asli Gulce Bartan
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Bilgehan Ibibik
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Tugce Bildik
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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İlayda Baydemir
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Hatice Asena Sanli
Basak Kayaoglu
Yasemin Ceylan
Tugce Yildirim
Irem Abras
Ihsan Cihan Ayanoglu
Sefa Burak Cam
Hacettepe University Histology and Bioengineering Departments Ankara Turkey
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Eda Ciftci Dede
Hacettepe University Histology and Bioengineering Departments Ankara Turkey
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Merve Gizer
Hacettepe University Histology and Bioengineering Departments Ankara Turkey
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Osman Erganis
Selcuk University Faculty of Veterinary Sciences Konya Turkey
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Fahriye Sarac
Istanbul Pendik Veteriner Kontrol Enstitusu
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Serdar Uzar
Istanbul Pendik Veteriner Kontrol Enstitusu
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Hakan Enul
Istanbul Pendik Veteriner Kontrol Enstitusu
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Cumhur Adiay
Istanbul Pendik Veteriner Kontrol Enstitusu
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Gamze Aykut
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Hivda Polat
Tubitak Marmara Arastirma Merkezi
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Ismail Selim Yildirim
Saban Tekin
Tubitak Marmara Arastirma Merkezi
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Hasan E. Zeytin
Nobel Ilac San ve Tic AS
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Petek Korkusuz
Hacettepe University Histology and Bioengineering Departments Ankara Turkey
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Ihsan Gursel
Bilkent University Molecular Biology and Genetics Department Ankara Turkey
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Mayda Gursel
Middle East Technical University Department of Biological Sciences Ankara Turkey
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Abstract

Background Vaccines that incorporate multiple SARS-CoV-2 antigens can further broaden the breadth of virus-specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS-CoV-2 VLP vaccine that incorporates the 4 structural proteins of SARS-CoV-2. Methods VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography and characterized by tunable resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. Results Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS-CoV-2. Alum adsorbed, K3-CpG ODN adjuvanted VLPs elicited high titer anti-S, anti-RBD, anti-N IgG, triggered multifunctional Th1 biased T cell responses, reduced virus load and prevented lung pathology upon live virus challenge in vaccinated animals. Conclusion These data suggest that VLPs expressing all four structural protein antigens of SARS-CoV-2 are immunogenic and can protect animals from developing COVID-19 infection following vaccination.
09 Jul 2021Submitted to Allergy
09 Jul 2021Submission Checks Completed
09 Jul 2021Assigned to Editor
13 Jul 2021Reviewer(s) Assigned
23 Jul 2021Review(s) Completed, Editorial Evaluation Pending
23 Jul 2021Editorial Decision: Revise Minor
06 Aug 20211st Revision Received
13 Aug 2021Submission Checks Completed
13 Aug 2021Assigned to Editor
13 Aug 2021Reviewer(s) Assigned
15 Aug 2021Review(s) Completed, Editorial Evaluation Pending
15 Aug 2021Editorial Decision: Accept