Chemically augmented malaria sporozoites display an altered immunogenic profile.

Autor:	Duszenko N; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands., van Schuijlenburg R; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Chevalley-Maurel S; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., van Willigen DM; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands., de Bes-Roeleveld L; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., van der Wees S; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Naar C; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Baalbergen E; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Heieis G; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Bunschoten A; Laboratory of BioNanoTechnology, Wageningen University & Research, Wageningen, Netherlands., Velders AH; Laboratory of BioNanoTechnology, Wageningen University & Research, Wageningen, Netherlands., Franke-Fayard B; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., van Leeuwen FWB; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands., Roestenberg M; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Aug 31; Vol. 14, pp. 1204606. Date of Electronic Publication: 2023 Aug 31 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1204606
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (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.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu