Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.

Abstract

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.

• 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 Roltgen, 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, Lara Doyle-Meyer, Rudolph B 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 Suthar, Neil P King, David Veesler, Bali Pulendran
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Feb 11 2021) United States
• PMID: 33594366 (Publication Type: Preprint)