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
Affiliations
Athanasios Blanas
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Haiko Karsjens
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Aafke de Ligt
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Elisabeth J.M. Huijbers
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Karlijn van Loon
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands
Stepan S. Denisov
School for Cardiovascular Sciences, Department of Biochemistry, Maastricht University, Maastricht, the Netherlands
Canan Durukan
Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Diederik J.M. Engbersen
CimCure BV, The Hague, the Netherlands
Jan Groen
Intravacc, Institute for Translational Vaccinology, Bilthoven, the Netherlands
Sven Hennig
Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Tilman M. Hackeng
School for Cardiovascular Sciences, Department of Biochemistry, Maastricht University, Maastricht, the Netherlands
Judy R. van Beijnum
CimCure BV, The Hague, the Netherlands
Arjan W. Griffioen
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Corresponding author
Summary: 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.
