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

Arunachalam, Prabhu S.; Walls, Alexandra C.; Golden, Nadia; Atyeo, Caroline; Fischinger, Stephanie; Li, Chunfeng; Aye, Pyone; Navarro, Mary Jane; Lai, Lilin; Edara, Venkata Viswanadh; Röltgen, Katharina; Rogers, Kenneth; Shirreff, Lisa; Ferrell, Douglas E; Wrenn, Samuel; Pettie, Deleah; Kraft, John C.; Miranda, Marcos C.; Kepl, Elizabeth; Sydeman, Claire; Brunette, Natalie; Murphy, Michael; Fiala, Brooke; Carter, Lauren; White, Alexander G; Trisal, Meera; Hsieh, Ching-Lin; Russell-Lodrigue, Kasi; Monjure, Christopher; Dufour, Jason; Doyle-Meyer, Lara; Bohm, Rudolph B.; Maness, Nicholas J.; Roy, Chad; Plante, Jessica A.; Plante, Kenneth S.; Zhu, Alex; Gorman, Matthew J.; Shin, Sally; Shen, Xiaoying; Fontenot, Jane; Gupta, Shakti; O’Hagan, Derek T.; Most, Robbert Van Der; Rappuoli, Rino; Coffman, Robert L.; Novack, David; McLellan, Jason S.; Subramaniam, Shankar; Montefiori, David; Boyd, Scott D.; Flynn, JoAnne L.; Alter, Galit; Villinger, Francois; Kleanthous, Harry; Rappaport, Jay; Suthar, Mehul; King, Neil P.; Veesler, David; Pulendran, Bali

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.