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 Sydeman, Natalie 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 Most, Rino Rappuoli, Robert L. Coffman, David Novack, Jason S. McLellan, Shankar Subramaniam, David Montefiori, Scott D. Boyd, JoAnne L. Flynn, Galit Alter, Francois Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, Neil P. King, David Veesler and Bali Pulendran ()
Additional contact information
Prabhu S. Arunachalam: Stanford University School of Medicine, Stanford University
Alexandra C. Walls: University of Washington
Nadia Golden: Tulane National Primate Research Center
Caroline Atyeo: Ragon Institute of MIT, MGH and Harvard
Stephanie Fischinger: Ragon Institute of MIT, MGH and Harvard
Chunfeng Li: Stanford University School of Medicine, Stanford University
Pyone Aye: Tulane National Primate Research Center
Mary Jane Navarro: University of Washington
Lilin Lai: Yerkes National Primate Research Center
Venkata Viswanadh Edara: Yerkes National Primate Research Center
Katharina Röltgen: Stanford University School of Medicine, Stanford University
Kenneth Rogers: University of Louisiana at Lafayette
Lisa Shirreff: University of Louisiana at Lafayette
Douglas E. Ferrell: University of Louisiana at Lafayette
Samuel Wrenn: University of Washington
Deleah Pettie: University of Washington
John C. Kraft: University of Washington
Marcos C. Miranda: University of Washington
Elizabeth Kepl: University of Washington
Claire Sydeman: University of Washington
Natalie Brunette: University of Washington
Michael Murphy: University of Washington
Brooke Fiala: University of Washington
Lauren Carter: University of Washington
Alexander G. White: University of Pittsburgh School of Medicine
Meera Trisal: Stanford University School of Medicine, Stanford University
Ching-Lin Hsieh: University of Texas
Kasi Russell-Lodrigue: Tulane National Primate Research Center
Christopher Monjure: Tulane National Primate Research Center
Jason Dufour: Tulane National Primate Research Center
Skye Spencer: Tulane National Primate Research Center
Lara Doyle-Meyers: Tulane National Primate Research Center
Rudolph P. Bohm: Tulane National Primate Research Center
Nicholas J. Maness: Tulane National Primate Research Center
Chad Roy: Tulane National Primate Research Center
Jessica A. Plante: University of Texas Medical Branch
Kenneth S. Plante: University of Texas Medical Branch
Alex Zhu: Ragon Institute of MIT, MGH and Harvard
Matthew J. Gorman: Ragon Institute of MIT, MGH and Harvard
Sally Shin: Ragon Institute of MIT, MGH and Harvard
Xiaoying Shen: Duke University School of Medicine
Jane Fontenot: University of Louisiana at Lafayette
Shakti Gupta: University of California, San Diego
Derek T. O’Hagan: GSK
Robbert Most: GSK
Rino Rappuoli: GSK
Robert L. Coffman: Dynavax Technologies Corporation
David Novack: Dynavax Technologies Corporation
Jason S. McLellan: University of Texas
Shankar Subramaniam: University of California, San Diego
David Montefiori: Duke University School of Medicine
Scott D. Boyd: Stanford University School of Medicine, Stanford University
JoAnne L. Flynn: University of Pittsburgh School of Medicine
Galit Alter: Ragon Institute of MIT, MGH and Harvard
Francois Villinger: University of Louisiana at Lafayette
Harry Kleanthous: Bill and Melinda Gates Foundation
Jay Rappaport: Tulane National Primate Research Center
Mehul S. Suthar: Yerkes National Primate Research Center
Neil P. King: University of Washington
David Veesler: University of Washington
Bali Pulendran: Stanford University School of Medicine, Stanford University

Nature, 2021, vol. 594, issue 7862, 253-258

Abstract: Abstract 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).

Date: 2021
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DOI: 10.1038/s41586-021-03530-2

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