Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

Lainscek, D.; Fink, T.; Forstneric, V.; Hafner-Bratkovic, I.; Orehek, S.; Strmsek, Z.; Mancek Keber, M.; Pecan, P.; Esih, H.; Malensek, S.; Aupic, J.; Dekleva, P.; Plaper, T.; Vidmar, S.; Kadunc, L.; Bencina, M.; Pojer, F.; Lau, K.; Hacker, D.; Correia, B.; Peterhoff, D.; Wagner, R.; Jerala, R.

doi:10.1101/2020.08.28.244269

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bioRxiv · 10.1101/2020.08.28.244269

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

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Abstract

Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and {beta}-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue {beta}-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

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Lainscek, D., Fink, T., Forstneric, V., Hafner-Bratkovic, I., Orehek, S., Strmsek, Z., Mancek Keber, M., Pecan, P., Esih, H., Malensek, S., Aupic, J., Dekleva, P., Plaper, T., Vidmar, S., Kadunc, L., Bencina, M., Pojer, F., Lau, K., Hacker, D., Correia, B., Peterhoff, D., Wagner, R., Jerala, R.. 2020-08-28. Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein. https://doi.org/10.1101/2020.08.28.244269

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