Adjuvanting a subunit COVID-19 vaccine to induce protective immunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-04-19

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

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). More... »

PAGES

253-258

Journal

TITLE

Nature

ISSUE

7862

VOLUME

594

Author Affiliations

  • Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA
  • Department of Biochemistry, University of Washington, Seattle, WA, USA
  • Tulane National Primate Research Center, Covington, LA, USA
  • Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA
  • Yerkes National Primate Research Center, Atlanta, Georgia, USA
  • Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA
  • New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA
  • Institute for Protein Design, University of Washington, Seattle, WA, USA
  • Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
  • Department of Molecular Biosciences, University of Texas, Austin, TX, USA
  • World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA
  • Department of Surgery, Duke University School of Medicine, Durham, NC, USA
  • Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
  • GSK, Rockville, MD, USA
  • GSK, Rixensart, Belgium
  • GSK, Siena, Italy
  • Dynavax Technologies Corporation, Emeryville, CA, USA
  • Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
  • Bill and Melinda Gates Foundation, Seattle, WA, USA
  • Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA
  • Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-021-03530-2

    DOI

    http://dx.doi.org/10.1038/s41586-021-03530-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1137302857

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33873199


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