Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Rajeshwer S. Sankhala; Kerri G. Lal; Jaime L. Jensen; Vincent Dussupt; Letzibeth Mendez-Rivera; Hongjun Bai; Lindsay Wieczorek; Sandra V. Mayer; Michelle Zemil; Danielle A. Wagner; Samantha M. Townsley; Agnes Hajduczki; William C. Chang; Wei Hung Chen; Gina C. Donofrio; Ningbo Jian; Hannah A.D. King; Cynthia G. Lorang; Elizabeth J. Martinez; Phyllis A. Rees; Caroline E. Peterson; Fabian Schmidt; Tricia J. Hart; Debra K. Duso; Lawrence W. Kummer; Sean P. Casey; Jazmean K. Williams; Shruthi Kannan; Bonnie M. Slike; Lauren Smith; Isabella Swafford; Paul V. Thomas; Ursula Tran; Jeffrey R. Currier; Diane L. Bolton; Edgar Davidson; Benjamin J. Doranz; Theodora Hatziioannou; Paul D. Bieniasz; Dominic Paquin-Proulx; William W. Reiley; Morgane Rolland; Nancy J. Sullivan; Sandhya Vasan; Natalie D. Collins; Kayvon Modjarrad; Gregory D. Gromowski; Victoria R. Polonis; Nelson L. Michael; Shelly J. Krebs; M. Gordon Joyce

doi:10.1038/s41467-023-44265-0

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Rajeshwer S. Sankhala, Kerri G. Lal, Jaime L. Jensen, Vincent Dussupt, Letzibeth Mendez-Rivera, Hongjun Bai, Lindsay Wieczorek, Sandra V. Mayer, Michelle Zemil, Danielle A. Wagner, Samantha M. Townsley, Agnes Hajduczki, William C. Chang, Wei Hung Chen, Gina C. Donofrio, Ningbo Jian, Hannah A.D. King, Cynthia G. Lorang, Elizabeth J. Martinez, Phyllis A. ReesCaroline E. Peterson, Fabian Schmidt, Tricia J. Hart, Debra K. Duso, Lawrence W. Kummer, Sean P. Casey, Jazmean K. Williams, Shruthi Kannan, Bonnie M. Slike, Lauren Smith, Isabella Swafford, Paul V. Thomas, Ursula Tran, Jeffrey R. Currier, Diane L. Bolton, Edgar Davidson, Benjamin J. Doranz, Theodora Hatziioannou, Paul D. Bieniasz, Dominic Paquin-Proulx, William W. Reiley, Morgane Rolland, Nancy J. Sullivan, Sandhya Vasan, Natalie D. Collins, Kayvon Modjarrad, Gregory D. Gromowski, Victoria R. Polonis, Nelson L. Michael, Shelly J. Krebs^*, M. Gordon Joyce^*

^*Corresponding author for this work

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

4 Scopus citations

Abstract

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Original language	English
Article number	200
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-44265-0
State	Published - Dec 2024
Externally published	Yes

Access to Document

10.1038/s41467-023-44265-0

Cite this

Sankhala, R. S., Lal, K. G., Jensen, J. L., Dussupt, V., Mendez-Rivera, L., Bai, H., Wieczorek, L., Mayer, S. V., Zemil, M., Wagner, D. A., Townsley, S. M., Hajduczki, A., Chang, W. C., Chen, W. H., Donofrio, G. C., Jian, N., King, H. A. D., Lorang, C. G., Martinez, E. J., ... Joyce, M. G. (2024). Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques. Nature Communications, 15(1), Article 200. https://doi.org/10.1038/s41467-023-44265-0

@article{80f1e45200c442b6a19aa3dd59c6ea81,

title = "Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques",

abstract = "The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.",

author = "Sankhala, {Rajeshwer S.} and Lal, {Kerri G.} and Jensen, {Jaime L.} and Vincent Dussupt and Letzibeth Mendez-Rivera and Hongjun Bai and Lindsay Wieczorek and Mayer, {Sandra V.} and Michelle Zemil and Wagner, {Danielle A.} and Townsley, {Samantha M.} and Agnes Hajduczki and Chang, {William C.} and Chen, {Wei Hung} and Donofrio, {Gina C.} and Ningbo Jian and King, {Hannah A.D.} and Lorang, {Cynthia G.} and Martinez, {Elizabeth J.} and Rees, {Phyllis A.} and Peterson, {Caroline E.} and Fabian Schmidt and Hart, {Tricia J.} and Duso, {Debra K.} and Kummer, {Lawrence W.} and Casey, {Sean P.} and Williams, {Jazmean K.} and Shruthi Kannan and Slike, {Bonnie M.} and Lauren Smith and Isabella Swafford and Thomas, {Paul V.} and Ursula Tran and Currier, {Jeffrey R.} and Bolton, {Diane L.} and Edgar Davidson and Doranz, {Benjamin J.} and Theodora Hatziioannou and Bieniasz, {Paul D.} and Dominic Paquin-Proulx and Reiley, {William W.} and Morgane Rolland and Sullivan, {Nancy J.} and Sandhya Vasan and Collins, {Natalie D.} and Kayvon Modjarrad and Gromowski, {Gregory D.} and Polonis, {Victoria R.} and Michael, {Nelson L.} and Krebs, {Shelly J.} and Joyce, {M. Gordon}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s41467-023-44265-0",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

number = "1",

}

Sankhala, RS, Lal, KG, Jensen, JL, Dussupt, V, Mendez-Rivera, L, Bai, H, Wieczorek, L, Mayer, SV, Zemil, M, Wagner, DA, Townsley, SM, Hajduczki, A, Chang, WC, Chen, WH, Donofrio, GC, Jian, N, King, HAD, Lorang, CG, Martinez, EJ, Rees, PA, Peterson, CE, Schmidt, F, Hart, TJ, Duso, DK, Kummer, LW, Casey, SP, Williams, JK, Kannan, S, Slike, BM, Smith, L, Swafford, I, Thomas, PV, Tran, U, Currier, JR, Bolton, DL, Davidson, E, Doranz, BJ, Hatziioannou, T, Bieniasz, PD, Paquin-Proulx, D, Reiley, WW, Rolland, M, Sullivan, NJ, Vasan, S, Collins, ND, Modjarrad, K, Gromowski, GD, Polonis, VR, Michael, NL, Krebs, SJ & Joyce, MG 2024, 'Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques', Nature Communications, vol. 15, no. 1, 200. https://doi.org/10.1038/s41467-023-44265-0

TY - JOUR

T1 - Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

AU - Sankhala, Rajeshwer S.

AU - Lal, Kerri G.

AU - Jensen, Jaime L.

AU - Dussupt, Vincent

AU - Mendez-Rivera, Letzibeth

AU - Bai, Hongjun

AU - Wieczorek, Lindsay

AU - Mayer, Sandra V.

AU - Zemil, Michelle

AU - Wagner, Danielle A.

AU - Townsley, Samantha M.

AU - Hajduczki, Agnes

AU - Chang, William C.

AU - Chen, Wei Hung

AU - Donofrio, Gina C.

AU - Jian, Ningbo

AU - King, Hannah A.D.

AU - Lorang, Cynthia G.

AU - Martinez, Elizabeth J.

AU - Rees, Phyllis A.

AU - Peterson, Caroline E.

AU - Schmidt, Fabian

AU - Hart, Tricia J.

AU - Duso, Debra K.

AU - Kummer, Lawrence W.

AU - Casey, Sean P.

AU - Williams, Jazmean K.

AU - Kannan, Shruthi

AU - Slike, Bonnie M.

AU - Smith, Lauren

AU - Swafford, Isabella

AU - Thomas, Paul V.

AU - Tran, Ursula

AU - Currier, Jeffrey R.

AU - Bolton, Diane L.

AU - Davidson, Edgar

AU - Doranz, Benjamin J.

AU - Hatziioannou, Theodora

AU - Bieniasz, Paul D.

AU - Paquin-Proulx, Dominic

AU - Reiley, William W.

AU - Rolland, Morgane

AU - Sullivan, Nancy J.

AU - Vasan, Sandhya

AU - Collins, Natalie D.

AU - Modjarrad, Kayvon

AU - Gromowski, Gregory D.

AU - Polonis, Victoria R.

AU - Michael, Nelson L.

AU - Krebs, Shelly J.

AU - Joyce, M. Gordon

PY - 2024/12

Y1 - 2024/12

N2 - The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

AB - The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

UR - http://www.scopus.com/inward/record.url?scp=85181258992&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-44265-0

DO - 10.1038/s41467-023-44265-0

M3 - Article

C2 - 38172512

AN - SCOPUS:85181258992

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 200

ER -

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Abstract

Access to Document

Fingerprint

Cite this