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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Author

Listed:
  • Prabhu S. Arunachalam

    (Stanford University School of Medicine, Stanford University)

  • Alexandra C. Walls

    (University of Washington)

  • Nadia Golden

    (Tulane National Primate Research Center)

  • Caroline Atyeo

    (Ragon Institute of MIT, MGH and Harvard)

  • Stephanie Fischinger

    (Ragon Institute of MIT, MGH and Harvard)

  • Chunfeng Li

    (Stanford University School of Medicine, Stanford University)

  • Pyone Aye

    (Tulane National Primate Research Center)

  • Mary Jane Navarro

    (University of Washington)

  • Lilin Lai

    (Yerkes National Primate Research Center)

  • Venkata Viswanadh Edara

    (Yerkes National Primate Research Center)

  • Katharina Röltgen

    (Stanford University School of Medicine, Stanford University)

  • Kenneth Rogers

    (University of Louisiana at Lafayette)

  • Lisa Shirreff

    (University of Louisiana at Lafayette)

  • Douglas E. Ferrell

    (University of Louisiana at Lafayette)

  • Samuel Wrenn

    (University of Washington
    University of Washington)

  • Deleah Pettie

    (University of Washington
    University of Washington)

  • John C. Kraft

    (University of Washington
    University of Washington)

  • Marcos C. Miranda

    (University of Washington
    University of Washington)

  • Elizabeth Kepl

    (University of Washington
    University of Washington)

  • Claire Sydeman

    (University of Washington
    University of Washington)

  • Natalie Brunette

    (University of Washington
    University of Washington)

  • Michael Murphy

    (University of Washington
    University of Washington)

  • Brooke Fiala

    (University of Washington
    University of Washington)

  • Lauren Carter

    (University of Washington
    University of Washington)

  • Alexander G. White

    (University of Pittsburgh School of Medicine
    University of Pittsburgh School of Medicine)

  • Meera Trisal

    (Stanford University School of Medicine, Stanford University)

  • Ching-Lin Hsieh

    (University of Texas)

  • Kasi Russell-Lodrigue

    (Tulane National Primate Research Center)

  • Christopher Monjure

    (Tulane National Primate Research Center)

  • Jason Dufour

    (Tulane National Primate Research Center)

  • Skye Spencer

    (Tulane National Primate Research Center)

  • Lara Doyle-Meyers

    (Tulane National Primate Research Center)

  • Rudolph P. Bohm

    (Tulane National Primate Research Center)

  • Nicholas J. Maness

    (Tulane National Primate Research Center)

  • Chad Roy

    (Tulane National Primate Research Center)

  • Jessica A. Plante

    (University of Texas Medical Branch)

  • Kenneth S. Plante

    (University of Texas Medical Branch)

  • Alex Zhu

    (Ragon Institute of MIT, MGH and Harvard)

  • Matthew J. Gorman

    (Ragon Institute of MIT, MGH and Harvard)

  • Sally Shin

    (Ragon Institute of MIT, MGH and Harvard)

  • Xiaoying Shen

    (Duke University School of Medicine)

  • Jane Fontenot

    (University of Louisiana at Lafayette)

  • Shakti Gupta

    (University of California, San Diego)

  • Derek T. O’Hagan

    (GSK)

  • Robbert Most

    (GSK)

  • Rino Rappuoli

    (GSK)

  • Robert L. Coffman

    (Dynavax Technologies Corporation)

  • David Novack

    (Dynavax Technologies Corporation)

  • Jason S. McLellan

    (University of Texas)

  • Shankar Subramaniam

    (University of California, San Diego)

  • David Montefiori

    (Duke University School of Medicine)

  • Scott D. Boyd

    (Stanford University School of Medicine, Stanford University)

  • JoAnne L. Flynn

    (University of Pittsburgh School of Medicine)

  • Galit Alter

    (Ragon Institute of MIT, MGH and Harvard)

  • Francois Villinger

    (University of Louisiana at Lafayette)

  • Harry Kleanthous

    (Bill and Melinda Gates Foundation)

  • Jay Rappaport

    (Tulane National Primate Research Center
    Tulane University School of Medicine)

  • Mehul S. Suthar

    (Yerkes National Primate Research Center)

  • Neil P. King

    (University of Washington
    University of Louisiana at Lafayette)

  • David Veesler

    (University of Washington)

  • Bali Pulendran

    (Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University)

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).

Suggested Citation

  • 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 Röltge, 2021. "Adjuvanting a subunit COVID-19 vaccine to induce protective immunity," Nature, Nature, vol. 594(7862), pages 253-258, June.
    • Handle: RePEc:nat:nature:v:594:y:2021:i:7862:d:10.1038_s41586-021-03530-2
    DOI: 10.1038/s41586-021-03530-2
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