TY - JOUR T1 - Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates JF - bioRxiv DO - 10.1101/2021.02.10.430696 SP - 2021.02.10.430696 AU - Prabhu S. Arunachalam AU - Alexandra C. Walls AU - Nadia Golden AU - Caroline Atyeo AU - Stephanie Fischinger AU - Chunfeng Li AU - Pyone Aye AU - Mary Jane Navarro AU - Lilin Lai AU - Venkata Viswanadh Edara AU - Katharina Röltgen AU - Kenneth Rogers AU - Lisa Shirreff AU - Douglas E Ferrell AU - Samuel Wrenn AU - Deleah Pettie AU - John C. Kraft AU - Marcos C. Miranda AU - Elizabeth Kepl AU - Claire Sydeman AU - Natalie Brunette AU - Michael Murphy AU - Brooke Fiala AU - Lauren Carter AU - Alexander G White AU - Meera Trisal AU - Ching-Lin Hsieh AU - Kasi Russell-Lodrigue AU - Christopher Monjure AU - Jason Dufour AU - Lara Doyle-Meyer AU - Rudolph B. Bohm AU - Nicholas J. Maness AU - Chad Roy AU - Jessica A. Plante AU - Kenneth S. Plante AU - Alex Zhu AU - Matthew J. Gorman AU - Sally Shin AU - Xiaoying Shen AU - Jane Fontenot AU - Shakti Gupta AU - Derek T. O’Hagan AU - Robbert Van Der Most AU - Rino Rappuoli AU - Robert L. Coffman AU - David Novack AU - Jason S. McLellan AU - Shankar Subramaniam AU - David Montefiori AU - Scott D. Boyd AU - JoAnne L. Flynn AU - Galit Alter AU - Francois Villinger AU - Harry Kleanthous AU - Jay Rappaport AU - Mehul Suthar AU - Neil P. King AU - David Veesler AU - Bali Pulendran Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/02/11/2021.02.10.430696.abstract N2 - 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.Competing Interest StatementDerek T. O Hagan, Robbert Van Der Most and Rino Rappuoli are employees of the GSK group of companies. Robert L. Coffman and David Novack are employees of Dynavax Technologies Corporation. Harry Kleanthous is an employee of the Bill and Melinda Gates Foundation. Ching-Lin Hsieh and Jason S. McLellan are inventors on U.S. patent application no. 63/032,502 Engineered Coronavirus Spike (S) Protein and Methods of Use Thereof. ER -