Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

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

Research output: Contribution to journalArticlepeer-review


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).

Original languageEnglish (US)
Pages (from-to)253-258
Number of pages6
Issue number7862
StatePublished - Jun 10 2021

ASJC Scopus subject areas

  • General


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