Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

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; Jo Anne L. Flynn; Galit Alter; Francois Villinger; Harry Kleanthous; Jay Rappaport; Mehul S. Suthar; Neil P. King; David Veesler; Bali Pulendran

doi:10.1038/s41586-021-03530-2

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

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 SydemanNatalie 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, Jo Anne L. Flynn, Galit Alter, Francois Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, Neil P. King, David Veesler, Bali Pulendran

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

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).

Original language	English (US)
Pages (from-to)	253-258
Number of pages	6
Journal	Nature
Volume	594
Issue number	7862
DOIs	https://doi.org/10.1038/s41586-021-03530-2
State	Published - Jun 10 2021

ASJC Scopus subject areas

General

Access to Document

10.1038/s41586-021-03530-2

Cite this

Arunachalam, P. S., Walls, A. C., Golden, N., Atyeo, C., Fischinger, S., Li, C., Aye, P., Navarro, M. J., Lai, L., Edara, V. V., Röltgen, K., Rogers, K., Shirreff, L., Ferrell, D. E., Wrenn, S., Pettie, D., Kraft, J. C., Miranda, M. C., Kepl, E., ... Pulendran, B. (2021). Adjuvanting a subunit COVID-19 vaccine to induce protective immunity. Nature, 594(7862), 253-258. https://doi.org/10.1038/s41586-021-03530-2

Arunachalam, PS, Walls, AC, Golden, N, Atyeo, C, Fischinger, S, Li, C, Aye, P, Navarro, MJ, Lai, L, Edara, VV, Röltgen, 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, Spencer, S, Doyle-Meyers, L, Bohm, RP, Maness, NJ, Roy, C, Plante, JA, Plante, KS, Zhu, A, Gorman, MJ, Shin, S, Shen, X, Fontenot, J, Gupta, S, O’Hagan, DT, Van Der Most, R, Rappuoli, R, Coffman, RL, Novack, D, McLellan, JS, Subramaniam, S, Montefiori, D, Boyd, SD, Flynn, JAL, Alter, G, Villinger, F, Kleanthous, H, Rappaport, J, Suthar, MS, King, NP, Veesler, D & Pulendran, B 2021, 'Adjuvanting a subunit COVID-19 vaccine to induce protective immunity', Nature, vol. 594, no. 7862, pp. 253-258. https://doi.org/10.1038/s41586-021-03530-2

@article{d1a6c413f1b945c3927b5ff4e544fe15,

title = "Adjuvanting a subunit COVID-19 vaccine to induce protective immunity",

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).",

author = "Arunachalam, {Prabhu S.} and Walls, {Alexandra C.} and Nadia Golden and Caroline Atyeo and Stephanie Fischinger and Chunfeng Li and Pyone Aye and Navarro, {Mary Jane} and Lilin Lai and Edara, {Venkata Viswanadh} and Katharina R{\"o}ltgen and Kenneth Rogers and Lisa Shirreff and Ferrell, {Douglas E.} and Samuel Wrenn and Deleah Pettie and Kraft, {John C.} and Miranda, {Marcos C.} and Elizabeth Kepl and Claire Sydeman and Natalie Brunette and Michael Murphy and Brooke Fiala and Lauren Carter and White, {Alexander G.} and Meera Trisal and Hsieh, {Ching Lin} and Kasi Russell-Lodrigue and Christopher Monjure and Jason Dufour and Skye Spencer and Lara Doyle-Meyers and Bohm, {Rudolph P.} and Maness, {Nicholas J.} and Chad Roy and Plante, {Jessica A.} and Plante, {Kenneth S.} and Alex Zhu and Gorman, {Matthew J.} and Sally Shin and Xiaoying Shen and Jane Fontenot and Shakti Gupta and O{\textquoteright}Hagan, {Derek T.} and {Van Der Most}, Robbert and Rino Rappuoli and Coffman, {Robert L.} and David Novack and McLellan, {Jason S.} and Shankar Subramaniam and David Montefiori and Boyd, {Scott D.} and Flynn, {Jo Anne L.} and Galit Alter and Francois Villinger and Harry Kleanthous and Jay Rappaport and Suthar, {Mehul S.} and King, {Neil P.} and David Veesler and Bali Pulendran",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jun,

day = "10",

doi = "10.1038/s41586-021-03530-2",

language = "English (US)",

volume = "594",

pages = "253--258",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7862",

}

TY - JOUR

T1 - Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

AU - Arunachalam, Prabhu S.

AU - Walls, Alexandra C.

AU - Golden, Nadia

AU - Atyeo, Caroline

AU - Fischinger, Stephanie

AU - Li, Chunfeng

AU - Aye, Pyone

AU - Navarro, Mary Jane

AU - Lai, Lilin

AU - Edara, Venkata Viswanadh

AU - Röltgen, Katharina

AU - Rogers, Kenneth

AU - Shirreff, Lisa

AU - Ferrell, Douglas E.

AU - Wrenn, Samuel

AU - Pettie, Deleah

AU - Kraft, John C.

AU - Miranda, Marcos C.

AU - Kepl, Elizabeth

AU - Sydeman, Claire

AU - Brunette, Natalie

AU - Murphy, Michael

AU - Fiala, Brooke

AU - Carter, Lauren

AU - White, Alexander G.

AU - Trisal, Meera

AU - Hsieh, Ching Lin

AU - Russell-Lodrigue, Kasi

AU - Monjure, Christopher

AU - Dufour, Jason

AU - Spencer, Skye

AU - Doyle-Meyers, Lara

AU - Bohm, Rudolph P.

AU - Maness, Nicholas J.

AU - Roy, Chad

AU - Plante, Jessica A.

AU - Plante, Kenneth S.

AU - Zhu, Alex

AU - Gorman, Matthew J.

AU - Shin, Sally

AU - Shen, Xiaoying

AU - Fontenot, Jane

AU - Gupta, Shakti

AU - O’Hagan, Derek T.

AU - Van Der Most, Robbert

AU - Rappuoli, Rino

AU - Coffman, Robert L.

AU - Novack, David

AU - McLellan, Jason S.

AU - Subramaniam, Shankar

AU - Montefiori, David

AU - Boyd, Scott D.

AU - Flynn, Jo Anne L.

AU - Alter, Galit

AU - Villinger, Francois

AU - Kleanthous, Harry

AU - Rappaport, Jay

AU - Suthar, Mehul S.

AU - King, Neil P.

AU - Veesler, David

AU - Pulendran, Bali

PY - 2021/6/10

Y1 - 2021/6/10

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=85104552468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85104552468&partnerID=8YFLogxK

U2 - 10.1038/s41586-021-03530-2

DO - 10.1038/s41586-021-03530-2

M3 - Article

C2 - 33873199

AN - SCOPUS:85104552468

SN - 0028-0836

VL - 594

SP - 253

EP - 258

JO - Nature

JF - Nature

IS - 7862

ER -

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this