Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates

S Arunachalam, P.; Walls, A. C.; Golden, N.; Atyeo, C.; Fischinger, S.; Li, C.; Aye, P.; Navarro, M. J.; Lai, L.; Edara, V. V.; Roltgen, K.; Rogers, K.; Shirreff, L.; Ferrell, D. E.; Wrenn, S.; Pettie, D.; Kraft, J. C.; Miranda, M. C.; Kepl, E.; Sydeman, C.; Brunette, N.; Murphy, M.; Fiala, B.; Carter, L.; White, A. G.; Trisal, M.; Hsieh, C.-L.; Russell-Lodrigue, K.; Monjure, C.; Dufour, J.; Doyle-Meyer, L.; Bohm, R. B.; Maness, N. J.; Roy, C.; Plante, J. A.; Plante, K. S.; Zhu, A.; Gorman, M. J.; Shin, S.; Shen, X.; Fontenot, J.; Gupta, S.; O Hagan, D. T.; Most, R. V. D.; Rappuoli, R.; Coffma

doi:10.1101/2021.02.10.430696

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bioRxiv · 10.1101/2021.02.10.430696

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates

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Abstract

The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.

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S Arunachalam, P., Walls, A. C., Golden, N., Atyeo, C., Fischinger, S., Li, C., Aye, P., Navarro, M. J., Lai, L., Edara, V. V., Roltgen, K., Rogers, K., Shirreff, L., Ferrell, D. E., Wrenn, S., Pettie, D., Kraft, J. C., Miranda, M. C., Kepl, E., Sydeman, C., Brunette, N., Murphy, M., Fiala, B., Carter, L., White, A. G., Trisal, M., Hsieh, C.-L., Russell-Lodrigue, K., Monjure, C., Dufour, J., Doyle-Meyer, L., Bohm, R. B., Maness, N. J., Roy, C., Plante, J. A., Plante, K. S., Zhu, A., Gorman, M. J., Shin, S., Shen, X., Fontenot, J., Gupta, S., O Hagan, D. T., Most, R. V. D., Rappuoli, R., Coffma. 2021-02-11. Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates. https://doi.org/10.1101/2021.02.10.430696

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