1. Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates
- Author
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Bali Pulendran, David Novack, Deleah Pettie, Jay Rappaport, Xiaoying Shen, Ching-Lin Hsieh, Rudolph B Bohm, Alexandra C. Walls, Elizabeth Kepl, David Veesler, Shankar Subramaniam, Rino Rappuoli, Harry Kleanthous, Claire Sydeman, Derek T O Hagan, Alex Lee Zhu, JoAnne L. Flynn, Robbert van der Most, Christopher Monjure, Kenneth S. Plante, Francois Villinger, Prabhu S. Arunachalam, Nicholas J. Maness, Pyone P. Aye, Sally Shin, Matthew J. Gorman, Natalie Brunette, Michael E. P. Murphy, Lilin Lai, Scott D. Boyd, Caroline Atyeo, Katharina Röltgen, Venkata Viswanadh Edara, Robert L Coffman, Chad J. Roy, Kasi E. Russell-Lodrigue, David C. Montefiori, Nadia A. Golden, Meera Trisal, Jessica A. Plante, John C. Kraft, Mehul S. Suthar, Jason Dufour, Kenneth A. Rogers, Marcos C. Miranda, Lisa Shirreff, Brooke Fiala, Samuel Wrenn, Lara Doyle-Meyer, Shakti Gupta, Douglas E. Ferrell, Jane Fontenot, Jason S. McLellan, Lauren Carter, Mary Jane Navarro, Alexander G. White, Stephanie Fischinger, Neil P. King, Galit Alter, and Chunfeng Li
- Subjects
Agonist ,Immunogen ,biology ,business.industry ,medicine.drug_class ,Alum ,medicine.medical_treatment ,Virology ,chemistry.chemical_compound ,Immunization ,chemistry ,Immunity ,medicine ,biology.protein ,AS03 ,business ,Neutralizing antibody ,Adjuvant - 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.
- Published
- 2021