Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques

Matthieu van Tilbeurgh; Pauline Maisonnasse; Jean-Louis Palgen; Monica Tolazzi; Yoann Aldon; Nathalie Dereuddre-Bosquet; Mariangela Cavarelli; Anne-Sophie Beignon; Ernesto Marcos-Lopez; Anne-Sophie Gallouet; Emmanuel Gilson; Gabriel Ozorowski; Andrew B. Ward; Ilja Bontjer; Paul F. McKay; Robin J. Shattock; Gabriella Scarlatti; Rogier W. Sanders; Roger le Grand

doi:https://doi.org/10.1016/j.xcrm.2022.100751

Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques

Matthieu van Tilbeurgh, Pauline Maisonnasse, Jean-Louis Palgen, Monica Tolazzi, Yoann Aldon, Nathalie Dereuddre-Bosquet, Mariangela Cavarelli, Anne-Sophie Beignon, Ernesto Marcos-Lopez, Anne-Sophie Gallouet, Emmanuel Gilson, Gabriel Ozorowski, Andrew B. Ward, Ilja Bontjer, Paul F. McKay, Robin J. Shattock, Gabriella Scarlatti, Rogier W. Sanders, Roger le Grand

Medical Microbiology and Infection Prevention (AMC)

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

1 Citation (Scopus)

Abstract

Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.

Original language	English
Article number	100751
Journal	Cell Reports Medicine
Volume	3
Issue number	10
DOIs	https://doi.org/10.1016/j.xcrm.2022.100751
Publication status	Published - 18 Oct 2022

Keywords

HIV vaccine
cynomolgus macaques
innate cells
mass cytometry
predictive model
system vaccinology

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https://doi.org/10.1016/j.xcrm.2022.100751

Cite this

van Tilbeurgh, M., Maisonnasse, P., Palgen, J.-L., Tolazzi, M., Aldon, Y., Dereuddre-Bosquet, N., Cavarelli, M., Beignon, A.-S., Marcos-Lopez, E., Gallouet, A.-S., Gilson, E., Ozorowski, G., Ward, A. B., Bontjer, I., McKay, P. F., Shattock, R. J., Scarlatti, G., Sanders, R. W., & le Grand, R. (2022). Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques. Cell Reports Medicine, 3(10), Article 100751. https://doi.org/10.1016/j.xcrm.2022.100751

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title = "Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques",

abstract = "Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.",

keywords = "HIV vaccine, cynomolgus macaques, innate cells, mass cytometry, predictive model, system vaccinology",

author = "{van Tilbeurgh}, Matthieu and Pauline Maisonnasse and Jean-Louis Palgen and Monica Tolazzi and Yoann Aldon and Nathalie Dereuddre-Bosquet and Mariangela Cavarelli and Anne-Sophie Beignon and Ernesto Marcos-Lopez and Anne-Sophie Gallouet and Emmanuel Gilson and Gabriel Ozorowski and Ward, {Andrew B.} and Ilja Bontjer and McKay, {Paul F.} and Shattock, {Robin J.} and Gabriella Scarlatti and Sanders, {Rogier W.} and {le Grand}, Roger",

note = "Funding Information: We thank the staff of the animal facility of IDMIT, particularly B. Delache, M. Pottier, S. Langlois, J.M. Robert, N. Dhooge, and R. Ho Tsong Fang. We also thank S. Kent, M. Hogarth, and B. Wines for providing the dimeric FcγRIIIa protein. Dietmar Katinger provided the adjuvants. This study was supported by the European Union's Horizon 2020 (EAVI2020, grant N°681137), the European Infrastructure TRANSVAC2 (grant N° 730964), the Agence Nationale de Recherche sur le SIDA et les h{\'e}patites virales (ANRS) and the Bill and Melinda Gates Foundation (OPP1115782). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organisation for Scientific Research (NWO). The Infectious Disease Models and Innovative Therapies Research Infrastructure (IDMIT) is supported by the “Programmes Investissements d'Avenir” (PIA), managed by the ANR under references ANR-11-INBS-0008 and ANR-10-EQPX-02-01. J.L.P. received a PhD scholarship from the University of Paris-Saclay. We thank the Fondation Dormeur Vaduz for the donation of instruments relevant to this project. A.B.W. and O.G. and performed electron microscopy experiments. A.S.B. contributed to the mass cytometry experiments design. A.S.G. coordinated the cytometry platform and experiments. E.G. contributed to the data analysis. E.M.L. managed the mass cytometer and contributed to the results analysis. G.S. contributed to the design of the study and the analysis of the data and coordinated the neutralization assays. I.B. designed and produced the immunogens. J.L.P. designed and supervised the mass cytometry experiments and contributed to the data analysis. M.C. coordinated the FcgR-binding assays and contributed to analysis of the data. M.T. performed the neutralization assays and analysis. M.V.T. performed the mass cytometry experiments, analyzed the data, and wrote the article. N.D.B. managed the ethical authorizations, prepared the vaccines, and contributed to the study design, to coordination, and to the data analyses. P.M. contributed to the design of the study, coordinated the study and experiments, prepared the vaccines, and contributed to the data analysis. P.M.K. supervised the ELISA experiments. R.L.G. contributed to the study design and the results analysis. R.J.S. coordinated the EAVI2020 project and contributed to the study design and to the results analysis. R.S. contributed to the study design and coordinated the immunogens production. Y.A. performed and analyzed the ELISA. All authors reviewed and edited the manuscript. The authors declare no competing interests. Funding Information: We thank the staff of the animal facility of IDMIT, particularly B. Delache, M. Pottier, S. Langlois, J.M. Robert, N. Dhooge, and R. Ho Tsong Fang. We also thank S. Kent, M. Hogarth, and B. Wines for providing the dimeric FcγRIIIa protein. Dietmar Katinger provided the adjuvants. This study was supported by the European Union{\textquoteright}s Horizon 2020 ( EAVI2020 , grant N°681137 ), the European Infrastructure TRANSVAC2 (grant N° 730964 ), the Agence Nationale de Recherche sur le SIDA et les h{\'e}patites virales ( ANRS ) and the Bill and Melinda Gates Foundation ( OPP1115782 ). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organisation for Scientific Research ( NWO ). The Infectious Disease Models and Innovative Therapies Research Infrastructure ( IDMIT ) is supported by the “ Programmes Investissements d{\textquoteright}Avenir ” (PIA), managed by the ANR under references ANR-11-INBS-0008 and ANR-10-EQPX-02-01 . J.L.P. received a PhD scholarship from the University of Paris-Saclay . We thank the Fondation Dormeur Vaduz for the donation of instruments relevant to this project. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = oct,

day = "18",

doi = "https://doi.org/10.1016/j.xcrm.2022.100751",

language = "English",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "10",

}

van Tilbeurgh, M, Maisonnasse, P, Palgen, J-L, Tolazzi, M, Aldon, Y, Dereuddre-Bosquet, N, Cavarelli, M, Beignon, A-S, Marcos-Lopez, E, Gallouet, A-S, Gilson, E, Ozorowski, G, Ward, AB, Bontjer, I, McKay, PF, Shattock, RJ, Scarlatti, G, Sanders, RW & le Grand, R 2022, 'Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques', Cell Reports Medicine, vol. 3, no. 10, 100751. https://doi.org/10.1016/j.xcrm.2022.100751

TY - JOUR

T1 - Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques

AU - van Tilbeurgh, Matthieu

AU - Maisonnasse, Pauline

AU - Palgen, Jean-Louis

AU - Tolazzi, Monica

AU - Aldon, Yoann

AU - Dereuddre-Bosquet, Nathalie

AU - Cavarelli, Mariangela

AU - Beignon, Anne-Sophie

AU - Marcos-Lopez, Ernesto

AU - Gallouet, Anne-Sophie

AU - Gilson, Emmanuel

AU - Ozorowski, Gabriel

AU - Ward, Andrew B.

AU - Bontjer, Ilja

AU - McKay, Paul F.

AU - Shattock, Robin J.

AU - Scarlatti, Gabriella

AU - Sanders, Rogier W.

AU - le Grand, Roger

N1 - Funding Information: We thank the staff of the animal facility of IDMIT, particularly B. Delache, M. Pottier, S. Langlois, J.M. Robert, N. Dhooge, and R. Ho Tsong Fang. We also thank S. Kent, M. Hogarth, and B. Wines for providing the dimeric FcγRIIIa protein. Dietmar Katinger provided the adjuvants. This study was supported by the European Union's Horizon 2020 (EAVI2020, grant N°681137), the European Infrastructure TRANSVAC2 (grant N° 730964), the Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) and the Bill and Melinda Gates Foundation (OPP1115782). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organisation for Scientific Research (NWO). The Infectious Disease Models and Innovative Therapies Research Infrastructure (IDMIT) is supported by the “Programmes Investissements d'Avenir” (PIA), managed by the ANR under references ANR-11-INBS-0008 and ANR-10-EQPX-02-01. J.L.P. received a PhD scholarship from the University of Paris-Saclay. We thank the Fondation Dormeur Vaduz for the donation of instruments relevant to this project. A.B.W. and O.G. and performed electron microscopy experiments. A.S.B. contributed to the mass cytometry experiments design. A.S.G. coordinated the cytometry platform and experiments. E.G. contributed to the data analysis. E.M.L. managed the mass cytometer and contributed to the results analysis. G.S. contributed to the design of the study and the analysis of the data and coordinated the neutralization assays. I.B. designed and produced the immunogens. J.L.P. designed and supervised the mass cytometry experiments and contributed to the data analysis. M.C. coordinated the FcgR-binding assays and contributed to analysis of the data. M.T. performed the neutralization assays and analysis. M.V.T. performed the mass cytometry experiments, analyzed the data, and wrote the article. N.D.B. managed the ethical authorizations, prepared the vaccines, and contributed to the study design, to coordination, and to the data analyses. P.M. contributed to the design of the study, coordinated the study and experiments, prepared the vaccines, and contributed to the data analysis. P.M.K. supervised the ELISA experiments. R.L.G. contributed to the study design and the results analysis. R.J.S. coordinated the EAVI2020 project and contributed to the study design and to the results analysis. R.S. contributed to the study design and coordinated the immunogens production. Y.A. performed and analyzed the ELISA. All authors reviewed and edited the manuscript. The authors declare no competing interests. Funding Information: We thank the staff of the animal facility of IDMIT, particularly B. Delache, M. Pottier, S. Langlois, J.M. Robert, N. Dhooge, and R. Ho Tsong Fang. We also thank S. Kent, M. Hogarth, and B. Wines for providing the dimeric FcγRIIIa protein. Dietmar Katinger provided the adjuvants. This study was supported by the European Union’s Horizon 2020 ( EAVI2020 , grant N°681137 ), the European Infrastructure TRANSVAC2 (grant N° 730964 ), the Agence Nationale de Recherche sur le SIDA et les hépatites virales ( ANRS ) and the Bill and Melinda Gates Foundation ( OPP1115782 ). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organisation for Scientific Research ( NWO ). The Infectious Disease Models and Innovative Therapies Research Infrastructure ( IDMIT ) is supported by the “ Programmes Investissements d’Avenir ” (PIA), managed by the ANR under references ANR-11-INBS-0008 and ANR-10-EQPX-02-01 . J.L.P. received a PhD scholarship from the University of Paris-Saclay . We thank the Fondation Dormeur Vaduz for the donation of instruments relevant to this project. Publisher Copyright: © 2022 The Author(s)

PY - 2022/10/18

Y1 - 2022/10/18

N2 - Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.

AB - Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.

KW - HIV vaccine

KW - cynomolgus macaques

KW - innate cells

KW - mass cytometry

KW - predictive model

KW - system vaccinology

UR - http://www.scopus.com/inward/record.url?scp=85140069814&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.xcrm.2022.100751

DO - https://doi.org/10.1016/j.xcrm.2022.100751

M3 - Article

C2 - 36167072

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 10

M1 - 100751

ER -

Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques

Abstract

Keywords

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