Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine

Arunachalam, P. S.; Feng, Y.; Ashraf, U.; Hu, M.; Edara, V. V.; Zarnitsyna, V. I.; Aye, P. P.; Golden, N.; Green, K. W. M.; Threeton, B. M.; Maness, N. J.; Beddingfield, B. J.; Bohm, R. P.; Dufour, J.; Russell-Lodrigue, K.; Miranda, M. C.; Walls, A. C.; Rogers, K.; Shirreff, L.; Ferrell, D. E.; Adhikary, N. R. D.; Fontenot, J.; Grifoni, A.; Sette, A.; O Hagan, D. T.; Most, R. V. D.; Rappuoli, R.; Villinger, F. J.; Kleanthous, H.; Rappaport, J.; Suthar, M. S.; Veesler, D.; Wang, T. T.; King, N. P.; Pulendran, B.

doi:10.1101/2022.03.18.484950

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bioRxiv · 10.1101/2022.03.18.484950

Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine

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Abstract

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-{beta} (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3x107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.

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Arunachalam, P. S., Feng, Y., Ashraf, U., Hu, M., Edara, V. V., Zarnitsyna, V. I., Aye, P. P., Golden, N., Green, K. W. M., Threeton, B. M., Maness, N. J., Beddingfield, B. J., Bohm, R. P., Dufour, J., Russell-Lodrigue, K., Miranda, M. C., Walls, A. C., Rogers, K., Shirreff, L., Ferrell, D. E., Adhikary, N. R. D., Fontenot, J., Grifoni, A., Sette, A., O Hagan, D. T., Most, R. V. D., Rappuoli, R., Villinger, F. J., Kleanthous, H., Rappaport, J., Suthar, M. S., Veesler, D., Wang, T. T., King, N. P., Pulendran, B.. 2022-03-20. Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine. https://doi.org/10.1101/2022.03.18.484950

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