Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.
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 protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD-NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD-NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD-NP in AS03 (RBD-NP-AS03), and correlated with protection from infection. RBD-NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD-NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD-NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD-NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD-NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
Arunachalam, PS; Walls, AC; Golden, N; Atyeo, C; Fischinger, S; Li, C; Aye, P; Navarro, MJ; Lai, L; Edara, VV; Röltgen, K; Rogers, K; Shirreff, L; Ferrell, DE; Wrenn, S; Pettie, D; Kraft, JC; Miranda, MC; Kepl, E; Sydeman, C; Brunette, N; Murphy, M; Fiala, B; Carter, L; White, AG; Trisal, M; Hsieh, C-L; Russell-Lodrigue, K; Monjure, C; Dufour, J; Spencer, S; Doyle-Meyers, L; Bohm, RP; Maness, NJ; Roy, C; Plante, JA; Plante, KS; Zhu, A; Gorman, MJ; Shin, S; Shen, X; Fontenot, J; Gupta, S; O'Hagan, DT; Van Der Most, R; Rappuoli, R; Coffman, RL; Novack, D; McLellan, JS; Subramaniam, S; Montefiori, D; Boyd, SD; Flynn, JL; Alter, G; Villinger, F; Kleanthous, H; Rappaport, J; Suthar, MS; King, NP; Veesler, D; Pulendran, B
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