1. Chemically augmented malaria sporozoites display an altered immunogenic profile
- Author
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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, and Meta Roestenberg
- Subjects
malaria ,vaccine ,adjuvant ,immunogenicity ,supramolecular chemistry ,Immunologic diseases. Allergy ,RC581-607 - 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.
- Published
- 2023
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