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Why is it important?

Despite the arsenal of COVID-19 vaccines, hospitalization and mortality associated with SARS-CoV-2 remain high. There is an urgent need to develop next-generation vaccines that provide broad protection against diseases by newly emerging variants, including Omicron. In this study, a mosaic multivalent nanoparticle, 6RBD-np, was created using six RBD domains linked to proliferating cell nuclear antigen heterotrimeric scaffolds. The immunization in human receptor-transgenic mice with the 6RBD-np elicited consistently high antibody responses against RBD antigens derived from the α- and β-coronaviruses and full-protection against the SARS-CoV-2 challenges. This study provides proof-of-concept that 6RBD-np induces 100% protection against SARS-CoV-2 challenges with the potential to induce broad inter-genus cross-reactivity.

Perspectives

Multivalent viral antigens are routinely made via protein engineering in a laboratory scale. A proof-of-concept for mosaic multivalent viral antigens presented in 2019, in which heterologous antigens are presented uniformly on nanoparticles, is taking a step further. However, currently used engineering platforms have significant drawbacks associated with employing a mixture of antigens to assemble mosaic nanoparticles. Co-display of heterologous antigens is particularly challenging in mass production, due to the difficulty to achieve a uniform distribution of antigens on nanoparticles. In this study, we present a possibility to create a true mosaic multivalent antigen, which induces 100% protection against SARS-CoV-2 challenges in a mouse model study with the potential to induce broad inter-genus cross-reactivity.

Kyung Hyun Kim
Korea University Sejong Campus

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This page is a summary of: Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge, Proceedings of the National Academy of Sciences, January 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2208425120.
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