Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

Counoupas, C.; Pino, P.; Stella, A.; Ashley, C.; Lukeman, H.; Bhattacharyya, N.; Tada, T.; Anchisi, S.; Metayer, C.; Martinis, J.; Aggarwal, A.; Dcosta, B.; Kint, J.; Wurm, M.; Landau, N.; Steain, M.; Turville, S.; Wurm, F.; David, S.; Triccas, J. A.

doi:10.1101/2021.08.18.456891

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bioRxiv · 10.1101/2021.08.18.456891

Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

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Abstract

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.

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Counoupas, C., Pino, P., Stella, A., Ashley, C., Lukeman, H., Bhattacharyya, N., Tada, T., Anchisi, S., Metayer, C., Martinis, J., Aggarwal, A., Dcosta, B., Kint, J., Wurm, M., Landau, N., Steain, M., Turville, S., Wurm, F., David, S., Triccas, J. A.. 2021-08-19. Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens. https://doi.org/10.1101/2021.08.18.456891

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