Abstract
The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.
Original language | English |
---|---|
Article number | 110143 |
Journal | Cell Reports |
Volume | 37 |
Issue number | 12 |
DOIs | |
State | Published - 21 Dec 2021 |
Externally published | Yes |
Keywords
- ALFQ
- B.1.1.7
- B.1.351
- COVID-19
- P.1
- SARS-CoV-1
- SARS-CoV-2
- betacoronaviruses
- ferritin nanoparticle
- neutralizing antibodies
- receptor-binding domain
- spike
- variants of concern
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SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity. / Joyce, M. Gordon; Chen, Wei Hung; Sankhala, Rajeshwer S. et al.
In: Cell Reports, Vol. 37, No. 12, 110143, 21.12.2021.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity
AU - Joyce, M. Gordon
AU - Chen, Wei Hung
AU - Sankhala, Rajeshwer S.
AU - Hajduczki, Agnes
AU - Thomas, Paul V.
AU - Choe, Misook
AU - Martinez, Elizabeth J.
AU - Chang, William C.
AU - Peterson, Caroline E.
AU - Morrison, Elaine B.
AU - Smith, Clayton
AU - Chen, Rita E.
AU - Ahmed, Aslaa
AU - Wieczorek, Lindsay
AU - Anderson, Alexander
AU - Case, James Brett
AU - Li, Yifan
AU - Oertel, Therese
AU - Rosado, Lorean
AU - Ganesh, Akshaya
AU - Whalen, Connor
AU - Carmen, Joshua M.
AU - Mendez-Rivera, Letzibeth
AU - Karch, Christopher P.
AU - Gohain, Neelakshi
AU - Villar, Zuzana
AU - McCurdy, David
AU - Beck, Zoltan
AU - Kim, Jiae
AU - Shrivastava, Shikha
AU - Jobe, Ousman
AU - Dussupt, Vincent
AU - Molnar, Sebastian
AU - Tran, Ursula
AU - Kannadka, Chandrika B.
AU - Soman, Sandrine
AU - Kuklis, Caitlin
AU - Zemil, Michelle
AU - Khanh, Htet
AU - Wu, Weimin
AU - Cole, Matthew A.
AU - Duso, Debra K.
AU - Kummer, Larry W.
AU - Lang, Tricia J.
AU - Muncil, Shania E.
AU - Currier, Jeffrey R.
AU - Krebs, Shelly J.
AU - Polonis, Victoria R.
AU - Rajan, Saravanan
AU - McTamney, Patrick M.
AU - Esser, Mark T.
AU - Reiley, William W.
AU - Rolland, Morgane
AU - de Val, Natalia
AU - Diamond, Michael S.
AU - Gromowski, Gregory D.
AU - Matyas, Gary R.
AU - Rao, Mangala
AU - Michael, Nelson L.
AU - Modjarrad, Kayvon
N1 - Funding Information: M.G.J. and K.M. are named as inventors on international patent application WO/2021/178971 A1 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is named as an inventor on international patent application WO/2018/081318 and U.S. patent 10,960,070 entitled “Prefusion coronavirus spike proteins and their use.” Z.B. is named as an inventor on U.S. patent 10,434,167 entitled “Non-toxic adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition and a saponin.” Z.B. and G.R.M. are named as inventors on U.S. patent application 16/607,917 entitled “Compositions and methods for vaccine delivery.” M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the scientific advisory boards of Moderna and Immunome. The Diamond laboratory has received funding support from sponsored research agreements from Moderna, Vir Biotechnology, Kaleido, and Emergent BioSolutions. S.R., P.M.M., and M.T.E. are employees of AstraZeneca and currently hold AstraZeneca stock or stock options. Z.B. is currently employed at Pfizer. Funding Information: Infectivity and neutralization titers were determined using ACE2-expressing HEK293 target cells (Integral Molecular) in a semi-automated assay format using robotic liquid handling (Biomek NXp Beckman Coulter). Test sera were diluted 1:40 in growth medium and serially diluted, then 25 μL/well was added to a white 96-well plate. An equal volume of diluted SARS-CoV-2 PSV was added to each well and plates were incubated for 1 hour at 37°C. Target cells were added to each well (40,000 cells/ well) and plates were incubated for an additional 48 hours. RLUs were measured with the EnVision Multimode Plate Reader (Perkin Elmer, Waltham, MA) using the Bright-Glo Luciferase Assay System (Promega Corporation, Madison, WI). Neutralization dose–response curves were fitted by nonlinear regression with a five-parameter curve fit using the LabKey Server® ( Piehler et al., 2011 ), and the final titers are reported as the reciprocal of the dilution of serum necessary to achieve 50% neutralization (ID50, 50% inhibitory dilution) and 80% neutralization (ID80, 80% inhibitory dilution). Assay equivalency for SARS-CoV-2 was established by participation in the SARS-CoV-2 Neutralizing Assay Concordance Survey (SNACS) run by the Virology Quality Assurance Program and External Quality Assurance Program Oversite Laboratory (EQAPOL) at the Duke Human Vaccine Institute, sponsored through programs supported by the National Institute of Allergy and Infectious Diseases, Division of AIDS. Funding Information: We thank Sandhya Vasan, Mihret Amare, Suzanne Mate, Paul Scott, and Sharon P. Daye for programmatic support and planning; Nathaniel Jackson for cell-culture maintenance; and Erin Kavusak and Jonah Heller for support with performance of the neutralization assays. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 1996 Edition. This work was funded by the U.S. Defense Health Agency , the U.S. Department of the Army , and a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense ( W81XWH-18-2-0040 ). This study also was supported by grants from the NIH ( R01 AI157155 ). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. The material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. Funding Information: We thank Sandhya Vasan, Mihret Amare, Suzanne Mate, Paul Scott, and Sharon P. Daye for programmatic support and planning; Nathaniel Jackson for cell-culture maintenance; and Erin Kavusak and Jonah Heller for support with performance of the neutralization assays. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 1996 Edition. This work was funded by the U.S. Defense Health Agency, the U.S. Department of the Army, and a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (W81XWH-18-2-0040). This study also was supported by grants from the NIH (R01 AI157155). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. The material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. M.G.J. and K.M. designed the study. M.G.J. P.V.T. and K.M. designed the immunogens. M.G.J. W.-H.C. M.C. R.S.S. A.H. P.V.T. R.E.C. W.C.C. C.E.P. E.B.M. E.J.M. A. Ahmed, C.S. J.B.C. Y.L. A. Anderson, J.K. T.O. L.R. A.G. C.W. J.M.C. L.M.-R. C.P.K. N.G. Z.V. D.M. Z.B. J.K. S. Shrivastava, O.J. V.D. S.M. U.T. C.B.K. S. Soman, C.K. M.Z. H.K. W.W. M.A.C. D.K.D. L.W.K. T.J.L. S.E.M. J.R.C. S.J.K. S.M. V.R.P. W.W.R. N.d.V. M.S.D. G.D.G. and M. Rao performed protein purification, biophysical assays, immunologic assays, and animal studies. Z.B. M. Rao, G.R.M. and A. Anderson designed and provided the adjuvants. S.R. P.M.M. and M.T.E. provided the SR1–SR5 antibodies. M.G.J. W.-H.C. R.S.S. A.H. P.V.T. R.E.C. C.S. A. Ahmed, L.W. Z.B. W.W. W.W.R. M. Rolland, N.d.V. M.S.D. G.D.G. M. Rao, N.L.M. and K.M. analyzed and interpreted the data. M.G.J. wrote the paper with assistance from all coauthors. M.G.J. and K.M. are named as inventors on international patent application WO/2021/178971 A1 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is named as an inventor on international patent application WO/2018/081318 and U.S. patent 10,960,070 entitled “Prefusion coronavirus spike proteins and their use.” Z.B. is named as an inventor on U.S. patent 10,434,167 entitled “Non-toxic adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition and a saponin.” Z.B. and G.R.M. are named as inventors on U.S. patent application 16/607,917 entitled “Compositions and methods for vaccine delivery.” M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation and on the scientific advisory boards of Moderna and Immunome. The Diamond laboratory has received funding support from sponsored research agreements from Moderna, Vir Biotechnology, Kaleido, and Emergent BioSolutions. S.R. P.M.M. and M.T.E. are employees of AstraZeneca and currently hold AstraZeneca stock or stock options. Z.B. is currently employed at Pfizer. Publisher Copyright: © 2021
PY - 2021/12/21
Y1 - 2021/12/21
N2 - The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.
AB - The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.
KW - ALFQ
KW - B.1.1.7
KW - B.1.351
KW - COVID-19
KW - P.1
KW - SARS-CoV-1
KW - SARS-CoV-2
KW - betacoronaviruses
KW - ferritin nanoparticle
KW - neutralizing antibodies
KW - receptor-binding domain
KW - spike
KW - variants of concern
UR - http://www.scopus.com/inward/record.url?scp=85121051681&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2021.110143
DO - 10.1016/j.celrep.2021.110143
M3 - Article
C2 - 34919799
AN - SCOPUS:85121051681
SN - 2211-1247
VL - 37
JO - Cell Reports
JF - Cell Reports
IS - 12
M1 - 110143
ER -