Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

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).

• Authors: 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 Van Der 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, Bali Pulendran
• Journal: Nature (Nature) Vol. 594 Issue 7862 Pg. 253-258 (06 2021) ISSN: 1476-4687 [Electronic] England
• PMID: 33873199 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Oligodeoxyribonucleotides
• Spike Glycoprotein, Coronavirus
• Vaccines, Subunit
• spike protein, SARS-CoV-2
• 1018 oligonucleotide
• aluminum sulfate
• Squalene

Topics

• Adjuvants, Immunologic
• Alum Compounds
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• CD4-Positive T-Lymphocytes (cytology, immunology)
• COVID-19 (immunology, prevention & control, virology)
• COVID-19 Vaccines (immunology)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Disease Models, Animal
• Immunity, Cellular
• Immunity, Humoral
• Macaca mulatta (immunology)
• Male
• Oligodeoxyribonucleotides
• SARS-CoV-2 (immunology)
• Spike Glycoprotein, Coronavirus (chemistry, immunology)
• Squalene
• Vaccines, Subunit (immunology)