In:
Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-8-31)
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 & lt; 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 & lt; 0.05), CD4 + T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p & lt; 0.05) and CD8 + T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p & lt; 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2023.1204606
DOI:
10.3389/fimmu.2023.1204606.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2606827-8
Permalink