Leiden University Scholarly Publications

Duszenko, N.; Schuijlenburg, R. van; Chevalley-Maurel, S.; Willigen, D.M. van; Bes-Roeleveld, L. de; Wees, S. van der; ... ; Roestenberg, M. (2023)

Chemically augmented malaria sporozoites display an altered immunogenic profile

Article / Letter to editor

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...Show more 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.
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malaria

vaccine

adjuvant

immunogenicity

supramolecular chemistry

All authors

Duszenko, N.; Schuijlenburg, R. van; Chevalley-Maurel, S.; Willigen, D.M. van; Bes-Roeleveld, L. de; Wees, S. van der; Naar, C.; Baalbergen, E.; Heieis, G.; Bunschoten, A.; Velders, A.H.; Franke-Fayard, B.; Leeuwen, F.W.B. van; Roestenberg, M.

Date

2023-08-31

Journal

Frontiers in Immunology

Volume

14

DOI

doi:10.3389/fimmu.2023.1204606

Link

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2...