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