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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity. Nature Arunachalam, P. S., 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., Russell-Lodrigue, K., Monjure, C., Dufour, J., Spencer, S., Doyle-Meyer, L., Bohm, R. P., 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., Van Der Most, R., Rappuoli, R., Coffman, R. L., Novack, D., McLellan, J. S., Subramaniam, S., Montefiori, D., Boyd, S. D., Flynn, J. L., Alter, G., Villinger, F., Kleanthous, H., Rappaport, J., Suthar, M. S., King, N. P., Veesler, D., Pulendran, B. 2021

Abstract

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike receptor binding domain displayed on a 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 adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing oil-in-water emulsion; AS37, a TLR-7 agonist adsorbed to Alum; CpG1018-Alum, a TLR-9 agonist formulated in Alum; and Alum. RBD-NP immunization with AS03, CpG1018-Alum, AS37 or Alum induced substantial nAb and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. Live-virus nAb response was maintained up to 180 days post-vaccination with RBD/AS03, and correlated with protection. RBD-NP immunization cross-neutralized the B.1.1.7 variant efficiently but showed a reduced response against the B.1.351 variant. While RBD-NP/AS03 demonstrated a 4.5-fold reduction in neutralization of B.1.351, the RBD-NP/AS37 group showed a 16-fold reduction, suggesting differences in the breadth of the nAb response induced by these adjuvants. Furthermore, RBD-NP/AS03 was as immunogenic as a prefusion stabilized Spike immunogen (Hexapro) adjuvanted with AS03. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2, and have paved the way for the clinical evaluation of this vaccine in Phase I/II clinical trials (NCT04742738 and NCT04750343).

View details for DOI 10.1038/s41586-021-03530-2

View details for PubMedID 33873199