Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

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Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses. / Brinkkemper, Mitch; Veth, Tim S.; Brouwer, Philip J. M. et al.

In: iScience, Vol. 25, No. 12, 105649, 22.12.2022.

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

BibTeX

@article{72dd0f0d0489438ba189eeba5670b992,

title = "Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses",

abstract = "The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses. Inclusion of Beta spike improved neutralizing antibody responses against SARS-CoV-2 Beta, Gamma, and Omicron BA.1 and BA.4/5. A third vaccination with ancestral SARS-CoV-2 spike also improved cross-neutralizing antibody responses against SARS-CoV-2 variants, in particular against the Omicron sublineages. Second, we combined SARS-CoV and SARS-CoV-2 spike proteins to broaden sarbecovirus immune responses. Adding SARS-CoV spike to a SARS-CoV-2 spike vaccine improved neutralizing responses against SARS-CoV and SARS-like bat sarbecoviruses SHC014 and WIV1. These results should inform the development of broadly active SARS-CoV-2 and pan-sarbecovirus vaccines and highlight the versatility of two-component nanoparticles for displaying diverse antigens.",

keywords = "Immune response, Immunology, Microbiology, Virology",

author = "Mitch Brinkkemper and Veth, {Tim S.} and Brouwer, {Philip J. M.} and Hannah Turner and Meliawati Poniman and Burger, {Judith A.} and Bouhuijs, {Joey H.} and Wouter Olijhoek and Ilja Bontjer and Snitselaar, {Jonne L.} and Caniels, {Tom G.} and {van der Linden}, {Cynthia A.} and Rashmi Ravichandran and Julien Villaudy and {van der Velden}, {Yme U.} and Kwinten Sliepen and {van Gils}, {Marit J.} and Ward, {Andrew B.} and King, {Neil P.} and Heck, {Albert J. R.} and Sanders, {Rogier W.}",

note = "Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1NL43ΔENV-NanoLuc and SARS-CoV-2-SΔ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research (NWO) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028. The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing—Original draft, Visualization, Project administration, M.B.; Conceptualization, Methodology, Investigation, Writing—Original draft, T.V.; Conceptualization, Methodology, Validation, Investigation, Project administration, P.J.M.B.; Investigation, Writing—Original draft, H.T.; Investigation, M.P.; J.A.B. J.H.B. I.B. C.A.v.d.L. R.R.; Conceptualization, Writing—Original draft, K.S.; Methodology, J.V.; Conceptualization, Methodology, Supervision, Project administration, Y.v.d.V.; Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, M.J.v.G.; Resources, Supervision, Writing—Review and editing, A.B.W. N.P.K. A.J.R.H.; Conceptualization, Validation, Resources, Writing—Review and editing, Supervision, Project administration, Funding acquisition, R.W.S. N.P.K. is a cofounder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs described in Brouwer et al.7 N.P.K. has a non-provisional US patent, no. 14/930,792, related to I53-50.53 All other authors declare no competing interests. Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research ( NWO ) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028 . The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = dec,

day = "22",

doi = "10.1016/j.isci.2022.105649",

language = "English",

volume = "25",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "12",

}

RIS

TY - JOUR

T1 - Co-display of diverse spike proteins on nanoparticles broadens sarbecovirus neutralizing antibody responses

AU - Brinkkemper, Mitch

AU - Veth, Tim S.

AU - Brouwer, Philip J. M.

AU - Turner, Hannah

AU - Poniman, Meliawati

AU - Burger, Judith A.

AU - Bouhuijs, Joey H.

AU - Olijhoek, Wouter

AU - Bontjer, Ilja

AU - Snitselaar, Jonne L.

AU - Caniels, Tom G.

AU - van der Linden, Cynthia A.

AU - Ravichandran, Rashmi

AU - Villaudy, Julien

AU - van der Velden, Yme U.

AU - Sliepen, Kwinten

AU - van Gils, Marit J.

AU - Ward, Andrew B.

AU - King, Neil P.

AU - Heck, Albert J. R.

AU - Sanders, Rogier W.

N1 - Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1NL43ΔENV-NanoLuc and SARS-CoV-2-SΔ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research (NWO) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923, OPP1132237, and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028. The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing—Original draft, Visualization, Project administration, M.B.; Conceptualization, Methodology, Investigation, Writing—Original draft, T.V.; Conceptualization, Methodology, Validation, Investigation, Project administration, P.J.M.B.; Investigation, Writing—Original draft, H.T.; Investigation, M.P.; J.A.B. J.H.B. I.B. C.A.v.d.L. R.R.; Conceptualization, Writing—Original draft, K.S.; Methodology, J.V.; Conceptualization, Methodology, Supervision, Project administration, Y.v.d.V.; Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, M.J.v.G.; Resources, Supervision, Writing—Review and editing, A.B.W. N.P.K. A.J.R.H.; Conceptualization, Validation, Resources, Writing—Review and editing, Supervision, Project administration, Funding acquisition, R.W.S. N.P.K. is a cofounder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. Amsterdam UMC has filed a patent application concerning the SARS-CoV-2 mAbs described in Brouwer et al.7 N.P.K. has a non-provisional US patent, no. 14/930,792, related to I53-50.53 All other authors declare no competing interests. Funding Information: We thank P. Bieniasz for kindly sharing the pHIV-1 NL43 ΔENV-NanoLuc and SARS-CoV-2-S Δ19 plasmids. We thank Dietmar Katinger and Philipp Mundsperger for providing the squalene emulsion adjuvant. This work was supported by a Netherlands Organization for Scientific Research ( NWO ) Vici grant (to R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1111923 , OPP1132237 , and INV-002022 (to R.W.S. and/or N.P.K.); by the Fondation Dormeur (to R.W.S. and to M.J.v.G.). M.J.v.G. is a recipient of an AMC Fellowship from Amsterdam UMC. A.J.R.H. acknowledges support from the Netherlands Organization for Scientific Research (NWO) through the Spinoza Award SPI.2017.028 . The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: © 2022 The Author(s)

PY - 2022/12/22

Y1 - 2022/12/22

N2 - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses. Inclusion of Beta spike improved neutralizing antibody responses against SARS-CoV-2 Beta, Gamma, and Omicron BA.1 and BA.4/5. A third vaccination with ancestral SARS-CoV-2 spike also improved cross-neutralizing antibody responses against SARS-CoV-2 variants, in particular against the Omicron sublineages. Second, we combined SARS-CoV and SARS-CoV-2 spike proteins to broaden sarbecovirus immune responses. Adding SARS-CoV spike to a SARS-CoV-2 spike vaccine improved neutralizing responses against SARS-CoV and SARS-like bat sarbecoviruses SHC014 and WIV1. These results should inform the development of broadly active SARS-CoV-2 and pan-sarbecovirus vaccines and highlight the versatility of two-component nanoparticles for displaying diverse antigens.

AB - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses continuous challenges in combating the virus. Here, we describe vaccination strategies to broaden SARS-CoV-2 and sarbecovirus immunity by combining spike proteins based on different viruses or viral strains displayed on two-component protein nanoparticles. First, we combined spike proteins based on ancestral and Beta SARS-CoV-2 strains to broaden SARS-CoV-2 immune responses. Inclusion of Beta spike improved neutralizing antibody responses against SARS-CoV-2 Beta, Gamma, and Omicron BA.1 and BA.4/5. A third vaccination with ancestral SARS-CoV-2 spike also improved cross-neutralizing antibody responses against SARS-CoV-2 variants, in particular against the Omicron sublineages. Second, we combined SARS-CoV and SARS-CoV-2 spike proteins to broaden sarbecovirus immune responses. Adding SARS-CoV spike to a SARS-CoV-2 spike vaccine improved neutralizing responses against SARS-CoV and SARS-like bat sarbecoviruses SHC014 and WIV1. These results should inform the development of broadly active SARS-CoV-2 and pan-sarbecovirus vaccines and highlight the versatility of two-component nanoparticles for displaying diverse antigens.

KW - Immune response

KW - Immunology

KW - Microbiology

KW - Virology

UR - http://www.scopus.com/inward/record.url?scp=85143506269&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2022.105649

DO - 10.1016/j.isci.2022.105649

M3 - Article

C2 - 36439375

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 12

M1 - 105649

ER -

ID: 28412297

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