Chemically augmented malaria sporozoites display an altered immunogenic profile

Despite promising results in malaria-naive 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-gamma production in liver-derived NK cells (percentage IFN-gamma(+) 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.