Chemically augmented malaria sporozoites display an altered immunogenic profile

Frontiers in Immunology

Immunology

Graham Heieis¹  Els Baalbergen¹  Roos van Schuijlenburg¹  Blandine Franke-Fayard¹  Severine Chevalley-Maurel¹  Meta Roestenberg¹  Laura de Bes-Roeleveld¹  Chanel Naar¹  Stefanie van der Wees¹  Nikolas Duszenko²  Fijs W. B. van Leeuwen³  Danny M. van Willigen³  Aldrik H. Velders⁴  Anton Bunschoten⁴ 

[1] Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands;Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands;Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands;Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands;Laboratory of BioNanoTechnology, Wageningen University & Research, Wageningen, Netherlands;

关键词: malaria;    vaccine;    adjuvant;    immunogenicity;    supramolecular chemistry;   

DOI  :  10.3389/fimmu.2023.1204606

 received in 2023-04-12, accepted in 2023-07-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Duszenko, van Schuijlenburg, Chevalley-Maurel, van Willigen, de Bes-Roeleveld, van der Wees, Naar, Baalbergen, Heieis, Bunschoten, Velders, Franke-Fayard, van Leeuwen and Roestenberg