Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Hannah A.D. King; M. Gordon Joyce; Ines Lakhal-Naouar; Aslaa Ahmed; Camila Macedo Cincotta; Caroline Subra; Kristina K. Peachman; Holly R. Hack; Rita E. Chen; Paul V. Thomas; Wei Hung Chen; Rajeshwer S. Sankhala; Agnes Hajduczki; Elizabeth J. Martinez; Caroline E. Peterson; William C. Chang; Misook Choe; Clayton Smith; Jarrett A. Headley; Hanne A. Elyard; Anthony Cook; Alexander Anderson; Kathryn McGuckin Wuertz; Ming Dong; Isabella Swafford; James B. Case; Jeffrey R. Currier; Kerri G. Lal; Mihret F. Amare; Vincent Dussupt; Sebastian Molnar; Sharon P. Daye; Xiankun Zeng; Erica K. Barkei; Kendra Alfson; Hilary M. Staples; Ricardo Carrion; Shelly J. Krebs; Dominic Paquin-Proulx; Nicos Karasavvas; Victoria R. Polonis; Linda L. Jagodzinski; Sandhya Vasan; Paul T. Scott; Yaoxing Huang; Manoj S. Nair; David D. Ho; Natalia de Val; Michael S. Diamond; Mark G. Lewis; Mangala Rao; Gary R. Matyas; Gregory D. Gromowski; Sheila A. Peel; Nelson L. Michael; Kayvon Modjarrad; Diane L. Bolton

doi:10.1073/pnas.2106433118

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Hannah A.D. King, M. Gordon Joyce, Ines Lakhal-Naouar, Aslaa Ahmed, Camila Macedo Cincotta, Caroline Subra, Kristina K. Peachman, Holly R. Hack, Rita E. Chen, Paul V. Thomas, Wei Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Elizabeth J. Martinez, Caroline E. Peterson, William C. Chang, Misook Choe, Clayton Smith, Jarrett A. Headley, Hanne A. ElyardAnthony Cook, Alexander Anderson, Kathryn McGuckin Wuertz, Ming Dong, Isabella Swafford, James B. Case, Jeffrey R. Currier, Kerri G. Lal, Mihret F. Amare, Vincent Dussupt, Sebastian Molnar, Sharon P. Daye, Xiankun Zeng, Erica K. Barkei, Kendra Alfson, Hilary M. Staples, Ricardo Carrion, Shelly J. Krebs, Dominic Paquin-Proulx, Nicos Karasavvas, Victoria R. Polonis, Linda L. Jagodzinski, Sandhya Vasan, Paul T. Scott, Yaoxing Huang, Manoj S. Nair, David D. Ho, Natalia de Val, Michael S. Diamond, Mark G. Lewis, Mangala Rao, Gary R. Matyas, Gregory D. Gromowski, Sheila A. Peel, Nelson L. Michael, Kayvon Modjarrad, Diane L. Bolton

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Abstract

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

Original language	English
Article number	e2106433118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	38
DOIs	https://doi.org/10.1073/pnas.2106433118
State	Published - Sep 21 2021

Keywords

Adjuvant
Macaque
Nanoparticle
SARS-CoV-2
Vaccine

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10.1073/pnas.2106433118

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King, H. A. D., Gordon Joyce, M., Lakhal-Naouar, I., Ahmed, A., Cincotta, C. M., Subra, C., Peachman, K. K., Hack, H. R., Chen, R. E., Thomas, P. V., Chen, W. H., Sankhala, R. S., Hajduczki, A., Martinez, E. J., Peterson, C. E., Chang, W. C., Choe, M., Smith, C., Headley, J. A., ... Bolton, D. L. (2021). Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques. Proceedings of the National Academy of Sciences of the United States of America, 118(38), Article e2106433118. https://doi.org/10.1073/pnas.2106433118

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title = "Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques",

abstract = "Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.",

keywords = "Adjuvant, Macaque, Nanoparticle, SARS-CoV-2, Vaccine",

author = "King, {Hannah A.D.} and {Gordon Joyce}, M. and Ines Lakhal-Naouar and Aslaa Ahmed and Cincotta, {Camila Macedo} and Caroline Subra and Peachman, {Kristina K.} and Hack, {Holly R.} and Chen, {Rita E.} and Thomas, {Paul V.} and Chen, {Wei Hung} and Sankhala, {Rajeshwer S.} and Agnes Hajduczki and Martinez, {Elizabeth J.} and Peterson, {Caroline E.} and Chang, {William C.} and Misook Choe and Clayton Smith and Headley, {Jarrett A.} and Elyard, {Hanne A.} and Anthony Cook and Alexander Anderson and {McGuckin Wuertz}, Kathryn and Ming Dong and Isabella Swafford and Case, {James B.} and Currier, {Jeffrey R.} and Lal, {Kerri G.} and Amare, {Mihret F.} and Vincent Dussupt and Sebastian Molnar and Daye, {Sharon P.} and Xiankun Zeng and Barkei, {Erica K.} and Kendra Alfson and Staples, {Hilary M.} and Ricardo Carrion and Krebs, {Shelly J.} and Dominic Paquin-Proulx and Nicos Karasavvas and Polonis, {Victoria R.} and Jagodzinski, {Linda L.} and Sandhya Vasan and Scott, {Paul T.} and Yaoxing Huang and Nair, {Manoj S.} and Ho, {David D.} and {de Val}, Natalia and Diamond, {Michael S.} and Lewis, {Mark G.} and Mangala Rao and Matyas, {Gary R.} and Gromowski, {Gregory D.} and Peel, {Sheila A.} and Michael, {Nelson L.} and Kayvon Modjarrad and Bolton, {Diane L.}",

year = "2021",

month = sep,

day = "21",

doi = "10.1073/pnas.2106433118",

language = "English",

volume = "118",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "38",

}

King, HAD, Gordon Joyce, M, Lakhal-Naouar, I, Ahmed, A, Cincotta, CM, Subra, C, Peachman, KK, Hack, HR, Chen, RE, Thomas, PV, Chen, WH, Sankhala, RS, Hajduczki, A, Martinez, EJ, Peterson, CE, Chang, WC, Choe, M, Smith, C, Headley, JA, Elyard, HA, Cook, A, Anderson, A, McGuckin Wuertz, K, Dong, M, Swafford, I, Case, JB, Currier, JR, Lal, KG, Amare, MF, Dussupt, V, Molnar, S, Daye, SP, Zeng, X, Barkei, EK, Alfson, K, Staples, HM, Carrion, R, Krebs, SJ, Paquin-Proulx, D, Karasavvas, N, Polonis, VR, Jagodzinski, LL, Vasan, S, Scott, PT, Huang, Y, Nair, MS, Ho, DD, de Val, N, Diamond, MS, Lewis, MG, Rao, M, Matyas, GR, Gromowski, GD, Peel, SA, Michael, NL, Modjarrad, K & Bolton, DL 2021, 'Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 38, e2106433118. https://doi.org/10.1073/pnas.2106433118

TY - JOUR

T1 - Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

AU - King, Hannah A.D.

AU - Gordon Joyce, M.

AU - Lakhal-Naouar, Ines

AU - Ahmed, Aslaa

AU - Cincotta, Camila Macedo

AU - Subra, Caroline

AU - Peachman, Kristina K.

AU - Hack, Holly R.

AU - Chen, Rita E.

AU - Thomas, Paul V.

AU - Chen, Wei Hung

AU - Sankhala, Rajeshwer S.

AU - Hajduczki, Agnes

AU - Martinez, Elizabeth J.

AU - Peterson, Caroline E.

AU - Chang, William C.

AU - Choe, Misook

AU - Smith, Clayton

AU - Headley, Jarrett A.

AU - Elyard, Hanne A.

AU - Cook, Anthony

AU - Anderson, Alexander

AU - McGuckin Wuertz, Kathryn

AU - Dong, Ming

AU - Swafford, Isabella

AU - Case, James B.

AU - Currier, Jeffrey R.

AU - Lal, Kerri G.

AU - Amare, Mihret F.

AU - Dussupt, Vincent

AU - Molnar, Sebastian

AU - Daye, Sharon P.

AU - Zeng, Xiankun

AU - Barkei, Erica K.

AU - Alfson, Kendra

AU - Staples, Hilary M.

AU - Carrion, Ricardo

AU - Krebs, Shelly J.

AU - Paquin-Proulx, Dominic

AU - Karasavvas, Nicos

AU - Polonis, Victoria R.

AU - Jagodzinski, Linda L.

AU - Vasan, Sandhya

AU - Scott, Paul T.

AU - Huang, Yaoxing

AU - Nair, Manoj S.

AU - Ho, David D.

AU - de Val, Natalia

AU - Diamond, Michael S.

AU - Lewis, Mark G.

AU - Rao, Mangala

AU - Matyas, Gary R.

AU - Gromowski, Gregory D.

AU - Peel, Sheila A.

AU - Michael, Nelson L.

AU - Modjarrad, Kayvon

AU - Bolton, Diane L.

PY - 2021/9/21

Y1 - 2021/9/21

N2 - Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

AB - Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

KW - Adjuvant

KW - Macaque

KW - Nanoparticle

KW - SARS-CoV-2

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85114916300&partnerID=8YFLogxK

U2 - 10.1073/pnas.2106433118

DO - 10.1073/pnas.2106433118

M3 - Article

C2 - 34470866

AN - SCOPUS:85114916300

SN - 0027-8424

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 38

M1 - e2106433118

ER -

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

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Keywords

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