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

bioRxiv, 2021-02

2021. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2021.02.10.430696v1 ;DOI: 10.1101/2021.02.10.430696

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Title:
Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates
Author: Arunachalam, Prabhu S ; Walls, Alexandra C ; Golden, Nadia ; Atyeo, Caroline ; Fischinger, Stephanie ; Li, Chunfeng ; Aye, Pyone ; Navarro, Mary Jane ; Lai, Lilin ; Edara, Venkata Viswanadh ; Röltgen, Katharina ; Rogers, Kenneth ; Shirreff, Lisa ; Ferrell, Douglas E ; Wrenn, Samuel ; Pettie, Deleah ; Kraft, John C ; Miranda, Marcos C ; Kepl, Elizabeth ; Sydeman, Claire ; Brunette, Natalie ; Murphy, Michael ; Fiala, Brooke ; Carter, Lauren ; White, Alexander G ; Trisal, Meera ; Ching-Lin, Hsieh ; Russell-Lodrigue, Kasi ; Monjure, Christopher ; Dufour, Jason ; Doyle-Meyer, Lara ; Bohm, Rudolph B ; Maness, Nicholas J ; Roy, Chad ; Plante, Jessica A ; Plante, Kenneth S ; Zhu, Alex ; Gorman, Matthew J ; Shin, Sally ; Shen, Xiaoying ; Fontenot, Jane ; Gupta, Shakti ; Derek T O’hagan ; Van Der Most, Robbert ; Rappuoli, Rino ; Coffman, Robert L ; Novack, David ; Mclellan, Jason S ; Subramaniam, Shankar ; Montefiori, David ; Boyd, Scott D ; Flynn, Joanne L ; Alter, Galit ; Villinger, Francois ; Kleanthous, Harry ; Rappaport, Jay ; Suthar, Mehul ; King, Neil P ; Veesler, David ; Bali Pulendran
Subjects: Adjuvants ; Agonists ; Alveoli ; Bronchus ; CD4 antigen ; Coronaviruses ; CpG islands ; Employees ; Immunization ; Influenza ; Lymphocytes T ; Nanoparticles ; Pandemics ; Patent applications ; Primates ; Proteins ; Public health ; Severe acute respiratory syndrome coronavirus 2 ; Spike protein ; Squalene ; TLR9 protein ; Toll-like receptors ; Vaccination ; Vaccines
Is Part Of: bioRxiv, 2021-02
Description: 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. Competing Interest Statement Derek T. O Hagan, Robbert Van Der Most and Rino Rappuoli are employees of the GSK group of companies. Robert L. Coffman and David Novack are employees of Dynavax Technologies Corporation. Harry Kleanthous is an employee of the Bill and Melinda Gates Foundation. Ching-Lin Hsieh and Jason S. McLellan are inventors on U.S. patent application no. 63/032,502 Engineered Coronavirus Spike (S) Protein and Methods of Use Thereof.
Publisher: Cold Spring Harbor: Cold Spring Harbor Laboratory Press
Language: English
Identifier: DOI: 10.1101/2021.02.10.430696
Source: Coronavirus Research Database

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

2021. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2021.02.10.430696v1 ;DOI: 10.1101/2021.02.10.430696

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