Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19

Athanasios Blanas; Haiko Karsjens; Aafke de Ligt; Elisabeth J.M. Huijbers; Karlijn van Loon; Stepan S. Denisov; Canan Durukan; Diederik J.M. Engbersen; Jan Groen; Sven Hennig; Tilman M. Hackeng; Judy R. van Beijnum; Arjan W. Griffioen

doi:10.1016/j.isci.2022.104719

Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19

Athanasios Blanas, Haiko Karsjens, Aafke de Ligt, Elisabeth J.M. Huijbers, Karlijn van Loon, Stepan S. Denisov, Canan Durukan, Diederik J.M. Engbersen, Jan Groen, Sven Hennig, Tilman M. Hackeng, Judy R. van Beijnum, Arjan W. Griffioen^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition of non- or low-immunogenic antigens, we developed a vaccine platform based on the conjugation of a target protein to a chimeric designer peptide (CDP) of bacterial origin. Here, we exploited this immune Boost (iBoost) technology to enhance the immune response against the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that the conjugation of CDP to RBD induced superior immune responses compared to RBD alone. CDP-RBD elicited cross-reactive antibodies against the variants of concern Delta and Omicron. Furthermore, hamsters vaccinated with CDP-RBD developed potent neutralizing antibody responses and were fully protected from lung lesion formation upon challenge with SARS-CoV-2. In sum, we show that the iBoost conjugate vaccine technology provides a valuable tool for both quantitatively and qualitatively enhancing anti-viral immunity.

Original language	English
Article number	104719
Pages (from-to)	1-19
Number of pages	20
Journal	iScience
Volume	25
Issue number	8
Early online date	5 Jul 2022
DOIs	https://doi.org/10.1016/j.isci.2022.104719
Publication status	Published - 19 Aug 2022

Bibliographical note

Funding Information:
This work was supported by the Dutch Top Sector Life Sciences and Health (Health Holland, project # LSHM20035 , to AWG, EH, and JvB) and the Dutch Cancer Society KWF (project # 2018-11651 , to AWG and EH).

Publisher Copyright:
© 2022 The Author(s)

Funding

This work was supported by the Dutch Top Sector Life Sciences and Health (Health Holland, project # LSHM20035 , to AWG, EH, and JvB) and the Dutch Cancer Society KWF (project # 2018-11651 , to AWG and EH).

Funders	Funder number
Dutch Cancer Society KWF	2018-11651
Dutch Top Sector Life Sciences and Health (Health Holland	LSHM20035

Keywords

Biological sciences
Immune response
Immunology
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2022.104719

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Blanas, A., Karsjens, H., de Ligt, A., Huijbers, E. J. M., van Loon, K., Denisov, S. S., Durukan, C., Engbersen, D. J. M., Groen, J., Hennig, S., Hackeng, T. M., van Beijnum, J. R., & Griffioen, A. W. (2022). Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19. iScience, 25(8), 1-19. Article 104719. https://doi.org/10.1016/j.isci.2022.104719

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title = "Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19",

abstract = "Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition of non- or low-immunogenic antigens, we developed a vaccine platform based on the conjugation of a target protein to a chimeric designer peptide (CDP) of bacterial origin. Here, we exploited this immune Boost (iBoost) technology to enhance the immune response against the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that the conjugation of CDP to RBD induced superior immune responses compared to RBD alone. CDP-RBD elicited cross-reactive antibodies against the variants of concern Delta and Omicron. Furthermore, hamsters vaccinated with CDP-RBD developed potent neutralizing antibody responses and were fully protected from lung lesion formation upon challenge with SARS-CoV-2. In sum, we show that the iBoost conjugate vaccine technology provides a valuable tool for both quantitatively and qualitatively enhancing anti-viral immunity.",

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note = "Funding Information: This work was supported by the Dutch Top Sector Life Sciences and Health (Health Holland, project # LSHM20035 , to AWG, EH, and JvB) and the Dutch Cancer Society KWF (project # 2018-11651 , to AWG and EH). Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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Blanas, A, Karsjens, H, de Ligt, A, Huijbers, EJM, van Loon, K, Denisov, SS, Durukan, C, Engbersen, DJM, Groen, J, Hennig, S, Hackeng, TM, van Beijnum, JR & Griffioen, AW 2022, 'Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19', iScience, vol. 25, no. 8, 104719, pp. 1-19. https://doi.org/10.1016/j.isci.2022.104719

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AU - Blanas, Athanasios

AU - Karsjens, Haiko

AU - de Ligt, Aafke

AU - Huijbers, Elisabeth J.M.

AU - van Loon, Karlijn

AU - Denisov, Stepan S.

AU - Durukan, Canan

AU - Engbersen, Diederik J.M.

AU - Groen, Jan

AU - Hennig, Sven

AU - Hackeng, Tilman M.

AU - van Beijnum, Judy R.

AU - Griffioen, Arjan W.

N1 - Funding Information: This work was supported by the Dutch Top Sector Life Sciences and Health (Health Holland, project # LSHM20035 , to AWG, EH, and JvB) and the Dutch Cancer Society KWF (project # 2018-11651 , to AWG and EH). Publisher Copyright: © 2022 The Author(s)

PY - 2022/8/19

Y1 - 2022/8/19

N2 - Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition of non- or low-immunogenic antigens, we developed a vaccine platform based on the conjugation of a target protein to a chimeric designer peptide (CDP) of bacterial origin. Here, we exploited this immune Boost (iBoost) technology to enhance the immune response against the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that the conjugation of CDP to RBD induced superior immune responses compared to RBD alone. CDP-RBD elicited cross-reactive antibodies against the variants of concern Delta and Omicron. Furthermore, hamsters vaccinated with CDP-RBD developed potent neutralizing antibody responses and were fully protected from lung lesion formation upon challenge with SARS-CoV-2. In sum, we show that the iBoost conjugate vaccine technology provides a valuable tool for both quantitatively and qualitatively enhancing anti-viral immunity.

AB - Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition of non- or low-immunogenic antigens, we developed a vaccine platform based on the conjugation of a target protein to a chimeric designer peptide (CDP) of bacterial origin. Here, we exploited this immune Boost (iBoost) technology to enhance the immune response against the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that the conjugation of CDP to RBD induced superior immune responses compared to RBD alone. CDP-RBD elicited cross-reactive antibodies against the variants of concern Delta and Omicron. Furthermore, hamsters vaccinated with CDP-RBD developed potent neutralizing antibody responses and were fully protected from lung lesion formation upon challenge with SARS-CoV-2. In sum, we show that the iBoost conjugate vaccine technology provides a valuable tool for both quantitatively and qualitatively enhancing anti-viral immunity.

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KW - Immunology

KW - Virology

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Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Persistent URL (handle)

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