Your browser doesn't support javascript.
loading
Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates
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.
Affiliation
  • Prabhu S Arunachalam; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Alexandra C Walls; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Nadia Golden; Tulane National Primate Research Center, Covington, LA, USA.
  • Caroline Atyeo; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Stephanie Fischinger; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA
  • Chunfeng Li; Stanford University
  • Pyone Aye; Tulane National Primate Research Center, Covington, LA, USA
  • Mary Jane Navarro; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lilin Lai; Yerkes National Primate Research Center, Atlanta, Georgia, USA.
  • Venkata Viswanadh Edara; Yerkes National Primate Research Center, Atlanta, Georgia, USA.
  • Katharina Roltgen; Stanford University
  • Kenneth Rogers; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Lisa Shirreff; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Douglas E Ferrell; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Samuel Wrenn; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Deleah Pettie; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • John C Kraft; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Marcos C Miranda; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Elizabeth Kepl; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Claire Sydeman; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Natalie Brunette; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Michael Murphy; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Brooke Fiala; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Lauren Carter; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Alexander G White; Department of Microbiology and Molecular Genetics and the Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Meera Trisal; Stanford University
  • Ching-Lin Hsieh; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Kasi Russell-Lodrigue; Tulane National Primate Research Center, Covington, LA, USA.
  • Christopher Monjure; Tulane National Primate Research Center, Covington, LA, USA.
  • Jason Dufour; Tulane National Primate Research Center, Covington, LA, USA.
  • Lara Doyle-Meyer; Tulane National Primate Research Center, Covington, LA, USA.
  • Rudolph B Bohm; Tulane National Primate Research Center, Covington, LA, USA.
  • Nicholas J Maness; Tulane National Primate Research Center, Covington, LA, USA.
  • Chad Roy; Tulane National Primate Research Center, Covington, LA, USA.
  • Jessica A Plante; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • Kenneth S Plante; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
  • Alex Zhu; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Matthew J Gorman; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Sally Shin; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Xiaoying Shen; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Jane Fontenot; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Shakti Gupta; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
  • Derek T O Hagan; GSK, Rockville, MD, USA.
  • Robbert Van Der Most; GSK, Rixensart, Belgium.
  • Rino Rappuoli; GSK, Siena, Italy.
  • Robert L Coffman; Dynavax Technologies Corporation, CA, USA.
  • David Novack; Dynavax Technologies Corporation, CA, USA.
  • Jason S McLellan; Department of Molecular Biosciences, University of Texas, Austin, TX 78712, USA.
  • Shankar Subramaniam; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
  • David Montefiori; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Scott D Boyd; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • JoAnne L Flynn; Department of Microbiology and Molecular Genetics and the Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Galit Alter; Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
  • Francois Villinger; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
  • Harry Kleanthous; Bill and Melinda Gates Foundation, Seattle, WA, USA.
  • Jay Rappaport; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
  • Mehul Suthar; Yerkes National Primate Research Center, Atlanta, Georgia, USA.
  • Neil P King; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • David Veesler; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Bali Pulendran; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Preprint in English | bioRxiv | ID: ppbiorxiv-430696
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.
License
cc_no
Fulltext
Add to My VHL
Print
XML
Search on Google
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint
Fulltext
Add to My VHL
Print
XML
Search on Google
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study / Rct Language: English Year: 2021 Document type: Preprint