Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection

Ismail Cem Yilmaz; Emre Mert Ipekoglu; Artun Bulbul; Nilsu Turay; Muzaffer Yildirim; Irem Evcili; Naz Surucu Yilmaz; Nese Guvencli; Yagmur Aydin; Bilgi Gungor; 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; Gulay Korukluoglu; Hasan Ersin Zeytin; Petek Korkusuz; Ihsan Gursel; Mayda Gursel

doi:10.1111/all.15091

Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection

Ismail Cem Yilmaz
, Emre Mert Ipekoglu
, Artun Bulbul
, Nilsu Turay
, Muzaffer Yildirim
, Irem Evcili
, Naz Surucu Yilmaz
, Nese Guvencli
, Yagmur Aydin
, Bilgi Gungor
, 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, Gulay Korukluoglu, Hasan Ersin Zeytin, Petek Korkusuz, Ihsan Gursel, Mayda Gursel

Division of Histology and Embryology (Medicine)

Middle East Technical University
Bilkent University
Hacettepe University
Selcuk University
Pendik Veterinary Research and Control Institute
Scientific and Technological Research Council of Turkey
General Directorate of Public Health
Nobel Pharma

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

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 four 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.

Original language	English
Pages (from-to)	258-270
Number of pages	13
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Volume	77
Issue number	1
DOIs	https://doi.org/10.1111/all.15091
Publication status	Published - Jan 2022

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SDG 3 Good Health and Well-being

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10.1111/all.15091

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Yilmaz, I. C., Ipekoglu, E. M., Bulbul, A., Turay, N., Yildirim, M., Evcili, I., Yilmaz, N. S., Guvencli, N., Aydin, Y., Gungor, B., Saraydar, B., Bartan, A. G., Ibibik, B., Bildik, T., Baydemir, İ., Sanli, H. A., Kayaoglu, B., Ceylan, Y., Yildirim, T., ... Gursel, M. (2022). Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection. Allergy: European Journal of Allergy and Clinical Immunology, 77(1), 258-270. https://doi.org/10.1111/all.15091

@article{e114064d304e4505878837b032b10880,

title = "Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection",

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 four 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.",

author = "Yilmaz, \{Ismail Cem\} and Ipekoglu, \{Emre Mert\} and Artun Bulbul and Nilsu Turay and Muzaffer Yildirim and Irem Evcili and Yilmaz, \{Naz Surucu\} and Nese Guvencli and Yagmur Aydin and Bilgi Gungor and Berfu Saraydar and Bartan, \{Asli Gulce\} and Bilgehan Ibibik and Tugce Bildik and İlayda Baydemir and Sanli, \{Hatice Asena\} and Basak Kayaoglu and Yasemin Ceylan and Tugce Yildirim and Irem Abras and Ayanoglu, \{Ihsan Cihan\} and Cam, \{Sefa Burak\} and \{Ciftci Dede\}, Eda and Merve Gizer and Osman Erganis and Fahriye Sarac and Serdar Uzar and Hakan Enul and Cumhur Adiay and Gamze Aykut and Hivda Polat and Yildirim, \{Ismail Selim\} and Saban Tekin and Gulay Korukluoglu and Zeytin, \{Hasan Ersin\} and Petek Korkusuz and Ihsan Gursel and Mayda Gursel",

note = "Publisher Copyright: {\textcopyright} 2021 European Academy of Allergy and Clinical Immunology and John Wiley \& Sons Ltd.",

year = "2022",

month = jan,

doi = "10.1111/all.15091",

language = "English",

volume = "77",

pages = "258--270",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "1",

}

Yilmaz, IC, Ipekoglu, EM, Bulbul, A, Turay, N, Yildirim, M, Evcili, I, Yilmaz, NS, Guvencli, N, Aydin, Y, Gungor, B, Saraydar, B, Bartan, AG, Ibibik, B, Bildik, T, Baydemir, İ, Sanli, HA, Kayaoglu, B, Ceylan, Y, Yildirim, T, Abras, I, Ayanoglu, IC, Cam, SB, Ciftci Dede, E, Gizer, M, Erganis, O, Sarac, F, Uzar, S, Enul, H, Adiay, C, Aykut, G, Polat, H, Yildirim, IS, Tekin, S, Korukluoglu, G, Zeytin, HE, Korkusuz, P, Gursel, I & Gursel, M 2022, 'Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection', Allergy: European Journal of Allergy and Clinical Immunology, vol. 77, no. 1, pp. 258-270. https://doi.org/10.1111/all.15091

TY - JOUR

T1 - Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection

AU - Yilmaz, Ismail Cem

AU - Ipekoglu, Emre Mert

AU - Bulbul, Artun

AU - Turay, Nilsu

AU - Yildirim, Muzaffer

AU - Evcili, Irem

AU - Yilmaz, Naz Surucu

AU - Guvencli, Nese

AU - Aydin, Yagmur

AU - Gungor, Bilgi

AU - Saraydar, Berfu

AU - Bartan, Asli Gulce

AU - Ibibik, Bilgehan

AU - Bildik, Tugce

AU - Baydemir, İlayda

AU - Sanli, Hatice Asena

AU - Kayaoglu, Basak

AU - Ceylan, Yasemin

AU - Yildirim, Tugce

AU - Abras, Irem

AU - Ayanoglu, Ihsan Cihan

AU - Cam, Sefa Burak

AU - Ciftci Dede, Eda

AU - Gizer, Merve

AU - Erganis, Osman

AU - Sarac, Fahriye

AU - Uzar, Serdar

AU - Enul, Hakan

AU - Adiay, Cumhur

AU - Aykut, Gamze

AU - Polat, Hivda

AU - Yildirim, Ismail Selim

AU - Tekin, Saban

AU - Korukluoglu, Gulay

AU - Zeytin, Hasan Ersin

AU - Korkusuz, Petek

AU - Gursel, Ihsan

AU - Gursel, Mayda

PY - 2022/1

Y1 - 2022/1

N2 - 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 four 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.

AB - 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 four 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.

UR - https://www.scopus.com/pages/publications/85115231660

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U2 - 10.1111/all.15091

DO - 10.1111/all.15091

M3 - Article

C2 - 34519053

AN - SCOPUS:85115231660

SN - 0105-4538

VL - 77

SP - 258

EP - 270

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 1

ER -

Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection

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