Chemically augmented malaria sporozoites display an altered immunogenic profile

Nikolas Duszenko; Roos van Schuijlenburg; Severine Chevalley-Maurel; Danny M. van Willigen; Laura de Bes-Roeleveld; Stefanie van der Wees; Chanel Naar; Els Baalbergen; Graham Heieis; Anton Bunschoten; Aldrik H. Velders; Blandine Franke-Fayard; Fijs W.B. van Leeuwen; Meta Roestenberg

doi:10.3389/fimmu.2023.1204606

Chemically augmented malaria sporozoites display an altered immunogenic profile

Nikolas Duszenko, Roos van Schuijlenburg, Severine Chevalley-Maurel, Danny M. van Willigen, Laura de Bes-Roeleveld, Stefanie van der Wees, Chanel Naar, Els Baalbergen, Graham Heieis, Anton Bunschoten, Aldrik H. Velders, Blandine Franke-Fayard, Fijs W.B. van Leeuwen, Meta Roestenberg^*

^*Corresponding author for this work

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

1 Citation (Scopus)

Abstract

Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ⁺ cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p < 0.05), CD4⁺ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p < 0.05) and CD8⁺ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.

Original language	English
Article number	1204606
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1204606
Publication status	Published - 2023

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

adjuvant
immunogenicity
malaria
supramolecular chemistry
vaccine

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https://edepot.wur.nl/639595Licence: CC BY

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Duszenko, N., van Schuijlenburg, R., Chevalley-Maurel, S., van Willigen, D. M., de Bes-Roeleveld, L., van der Wees, S., Naar, C., Baalbergen, E., Heieis, G., Bunschoten, A., Velders, A. H., Franke-Fayard, B., van Leeuwen, F. W. B., & Roestenberg, M. (2023). Chemically augmented malaria sporozoites display an altered immunogenic profile. Frontiers in Immunology, 14, Article 1204606. https://doi.org/10.3389/fimmu.2023.1204606

@article{78da7df45c6345dbafa4feab13ad40db,

title = "Chemically augmented malaria sporozoites display an altered immunogenic profile",

abstract = "Despite promising results in malaria-na{\"i}ve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ+ cells 11.1 ± 1.8 vs. 9.4 ± 1.5\%, p < 0.05), CD4+ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7\%, p < 0.05) and CD8+ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9\%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.",

keywords = "adjuvant, immunogenicity, malaria, supramolecular chemistry, vaccine",

author = "Nikolas Duszenko and \{van Schuijlenburg\}, Roos and Severine Chevalley-Maurel and \{van Willigen\}, \{Danny M.\} and \{de Bes-Roeleveld\}, Laura and \{van der Wees\}, Stefanie and Chanel Naar and Els Baalbergen and Graham Heieis and Anton Bunschoten and Velders, \{Aldrik H.\} and Blandine Franke-Fayard and \{van Leeuwen\}, \{Fijs W.B.\} and Meta Roestenberg",

year = "2023",

doi = "10.3389/fimmu.2023.1204606",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media",

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Duszenko, N, van Schuijlenburg, R, Chevalley-Maurel, S, van Willigen, DM, de Bes-Roeleveld, L, van der Wees, S, Naar, C, Baalbergen, E, Heieis, G, Bunschoten, A , Velders, AH, Franke-Fayard, B, van Leeuwen, FWB & Roestenberg, M 2023, 'Chemically augmented malaria sporozoites display an altered immunogenic profile', Frontiers in Immunology, vol. 14, 1204606. https://doi.org/10.3389/fimmu.2023.1204606

TY - JOUR

T1 - Chemically augmented malaria sporozoites display an altered immunogenic profile

AU - Duszenko, Nikolas

AU - van Schuijlenburg, Roos

AU - Chevalley-Maurel, Severine

AU - van Willigen, Danny M.

AU - de Bes-Roeleveld, Laura

AU - van der Wees, Stefanie

AU - Naar, Chanel

AU - Baalbergen, Els

AU - Heieis, Graham

AU - Bunschoten, Anton

AU - Velders, Aldrik H.

AU - Franke-Fayard, Blandine

AU - van Leeuwen, Fijs W.B.

AU - Roestenberg, Meta

PY - 2023

Y1 - 2023

N2 - Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ+ cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p < 0.05), CD4+ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p < 0.05) and CD8+ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.

AB - Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ+ cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p < 0.05), CD4+ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p < 0.05) and CD8+ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.

KW - adjuvant

KW - immunogenicity

KW - malaria

KW - supramolecular chemistry

KW - vaccine

U2 - 10.3389/fimmu.2023.1204606

DO - 10.3389/fimmu.2023.1204606

M3 - Article

C2 - 37720224

AN - SCOPUS:85170667088

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1204606

ER -

Chemically augmented malaria sporozoites display an altered immunogenic profile

Abstract

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Keywords

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