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

iScience. 2022 Aug 19;25(8):104719. doi: 10.1016/j.isci.2022.104719. Epub 2022 Jul 5.

Affiliations

¹ Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
² School for Cardiovascular Sciences, Department of Biochemistry, Maastricht University, Maastricht, the Netherlands.
³ Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁴ CimCure BV, The Hague, the Netherlands.
⁵ Intravacc, Institute for Translational Vaccinology, Bilthoven, the Netherlands.

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.

Keywords: Biological sciences; Immune response; Immunology; Virology.