A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Counoupas, C.; Pino, P.; Armitano, J.; Johansen, M.; Smith, L.; Chan, E.; Ashley, C.; Estape, E.; Troyon, J.; Alca, S.; Miemczyk, S.; Hansbro, N.; Scandurra, G.; Britton, W. J.; Courant, T.; Dubois, P.; Collin, N.; Mohan, V. K.; Hansbro, P. M.; Wurm, M.; Wurm, F.; Steain, M.; Triccas, J.

doi:10.1101/2024.11.06.622391

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bioRxiv · 10.1101/2024.11.06.622391

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

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Abstract

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

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Counoupas, C., Pino, P., Armitano, J., Johansen, M., Smith, L., Chan, E., Ashley, C., Estape, E., Troyon, J., Alca, S., Miemczyk, S., Hansbro, N., Scandurra, G., Britton, W. J., Courant, T., Dubois, P., Collin, N., Mohan, V. K., Hansbro, P. M., Wurm, M., Wurm, F., Steain, M., Triccas, J.. 2024-11-07. A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity. https://doi.org/10.1101/2024.11.06.622391

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