Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Prabhu S Arunachalam¹, Alexandra C Walls², Nadia Golden³, Caroline Atyeo⁴, Stephanie Fischinger⁴, Chunfeng Li¹, Pyone Aye³, Mary Jane Navarro², Lilin Lai⁵, Venkata Viswanadh Edara⁵, Katharina Röltgen⁶, Kenneth Rogers⁷, Lisa Shirreff⁷, Douglas E Ferrell⁷, Samuel Wrenn^{2

8}, Deleah Pettie^{2

8}, John C Kraft^{2

8}, Marcos C Miranda^{2

8}, Elizabeth Kepl^{2

8}, Claire Sydeman^{2

8}, Natalie Brunette^{2

8}, Michael Murphy^{2

8}, Brooke Fiala^{2

8}, Lauren Carter^{2

8}, Alexander G White^{9

10}, Meera Trisal¹, Ching-Lin Hsieh¹¹, Kasi Russell-Lodrigue³, Christopher Monjure³, Jason Dufour³, Skye Spencer³, Lara Doyle-Meyers³, Rudolph P Bohm³, Nicholas J Maness³, Chad Roy³, Jessica A Plante¹², Kenneth S Plante¹², Alex Zhu⁴, Matthew J Gorman⁴, Sally Shin⁴, Xiaoying Shen¹³, Jane Fontenot⁷, Shakti Gupta¹⁴, Derek T O'Hagan¹⁵, Robbert Van Der Most¹⁶, Rino Rappuoli¹⁷, Robert L Coffman¹⁸, David Novack¹⁸, Jason S McLellan¹¹, Shankar Subramaniam¹⁴, David Montefiori¹³, Scott D Boyd⁶, JoAnne L Flynn⁹, Galit Alter⁴, Francois Villinger⁷, Harry Kleanthous¹⁹, Jay Rappaport^{3

20}, Mehul S Suthar⁵, Neil P King^{2

7}, David Veesler², Bali Pulendran^{21

22

23}

Affiliations

¹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
² Department of Biochemistry, University of Washington, Seattle, WA, USA.
³ Tulane National Primate Research Center, Covington, LA, USA.
⁴ Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
⁵ Yerkes National Primate Research Center, Atlanta, Georgia, USA.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
⁷ New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
⁸ Institute for Protein Design, University of Washington, Seattle, WA, USA.
⁹ Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹¹ Department of Molecular Biosciences, University of Texas, Austin, TX, USA.
¹² World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
¹³ Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
¹⁴ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
¹⁵ GSK, Rockville, MD, USA.
¹⁶ GSK, Rixensart, Belgium.
¹⁷ GSK, Siena, Italy.
¹⁸ Dynavax Technologies Corporation, Emeryville, CA, USA.
¹⁹ Bill and Melinda Gates Foundation, Seattle, WA, USA.
²⁰ Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
²¹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
²² Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
²³ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.

PMID: 33873199
DOI: 10.1038/s41586-021-03530-2

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Prabhu S Arunachalam et al. Nature. 2021 Jun.

. 2021 Jun;594(7862):253-258.

doi: 10.1038/s41586-021-03530-2. Epub 2021 Apr 19.

Authors

Affiliations

¹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
² Department of Biochemistry, University of Washington, Seattle, WA, USA.
³ Tulane National Primate Research Center, Covington, LA, USA.
⁴ Ragon Institute of MIT, MGH and Harvard, Cambridge, MA, USA.
⁵ Yerkes National Primate Research Center, Atlanta, Georgia, USA.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
⁷ New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.
⁸ Institute for Protein Design, University of Washington, Seattle, WA, USA.
⁹ Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹¹ Department of Molecular Biosciences, University of Texas, Austin, TX, USA.
¹² World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.
¹³ Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
¹⁴ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
¹⁵ GSK, Rockville, MD, USA.
¹⁶ GSK, Rixensart, Belgium.
¹⁷ GSK, Siena, Italy.
¹⁸ Dynavax Technologies Corporation, Emeryville, CA, USA.
¹⁹ Bill and Melinda Gates Foundation, Seattle, WA, USA.
²⁰ Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.
²¹ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
²² Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.
²³ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. bpulend@stanford.edu.

PMID: 33873199
DOI: 10.1038/s41586-021-03530-2

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).

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Update of

Adjuvanting a subunit SARS-CoV-2 nanoparticle vaccine to induce protective immunity in non-human primates.
S Arunachalam P, Walls AC, Golden N, Atyeo C, Fischinger S, Li C, Aye P, Navarro MJ, Lai L, Edara VV, Roltgen K, Rogers K, Shirreff L, Ferrell DE, Wrenn S, Pettie D, Kraft JC, Miranda MC, Kepl E, Sydeman C, Brunette N, Murphy M, Fiala B, Carter L, White AG, Trisal M, Hsieh CL, Russell-Lodrigue K, Monjure C, Dufour J, Doyle-Meyer L, Bohm RB, Maness NJ, Roy C, Plante JA, Plante KS, Zhu A, Gorman MJ, Shin S, Shen X, Fontenot J, Gupta S, O Hagan DT, Most RV, Rappuoli R, Coffman RL, Novack D, McLellan JS, Subramaniam S, Montefiori D, Boyd SD, Flynn JL, Alter G, Villinger F, Kleanthous H, Rappaport J, Suthar M, King NP, Veesler D, Pulendran B. S Arunachalam P, et al. bioRxiv [Preprint]. 2021 Feb 11:2021.02.10.430696. doi: 10.1101/2021.02.10.430696. bioRxiv. 2021. Update in: Nature. 2021 Jun;594(7862):253-258. doi: 10.1038/s41586-021-03530-2. PMID: 33594366 Free PMC article. Updated. Preprint.

References

1. Krammer, F. SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020). - PubMed - DOI
1. Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2021). - PubMed - DOI
1. Pulendran, B., S Arunachalam, P. & O’Hagan, D. T. Emerging concepts in the science of vaccine adjuvants. Nat. Rev. Drug Discov. https://doi.org/10.1038/s41573-021-00163-y (2021).
1. Thanh Le, T. et al. The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 19, 305–306 (2020). - PubMed - DOI
1. Walls, A. C. et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell 183, 1367–1382 (2020). - PubMed - PMC - DOI

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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Affiliations

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Authors

Affiliations

Abstract

Update of

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

Research Materials

Miscellaneous