Carbohydrate-Modified Virus-Like Particles as a Vaccine Platform for Leishmania braziliensis 2247392

Abstract

Abstract Introduction Leishmania braziliensis is an important etiological agent of cutaneous leishmaniasis in the Americas, and it is associated with chronic lesions, tissue destruction, and severe morbidity. The toxicity, incomplete efficacy, and development of resistance associated with current chemotherapeutics emphasize the critical need for new immunoprophylactic approaches. Methods We tested the protective effect of a virus-like particle (VLP) platform that was recombinantly engineered to present the α-galactosyl (α-Gal) epitope, a carbohydrate recognized by natural anti-carbohydrate immune responses against L. braziliensis infection in mice. Mice were primed with empty Qβ VLPs (Qβ-WT), Qβ-αGal VLPs, or controls (PBS and naïve). Results Lesions were followed for 18 weeks post infection by footpad swelling. Qβ-αGal-vaccinated animals showed smaller lesion size than Qβ-WT and PBS controls, which presented swelling and severe pathology. Histological evaluation showed reduction in tissue damage in Qβ-αGal—immunized animals. Unvaccinated mice presented a much higher parasite load compared to Qβ-αGal—vaccinated animals. Spleen supernatant was analyzed, whose protection was correlated with the induction of Th1-related cytokines by increased IFN-γ and IL-12 in Qβ-αGal—immunized mice. These cytokines are essential for macrophage activation and parasite killing, implying that α-Gal—decorated VLPs induce a protective immune response. Qβ-WT and PBS showed little effect on cytokine induction, while lesions grew. Conclusion Our results provide proof of concept for the ability of α-Gal-conjugated VLP to induce a protective immune response against L. braziliensis infection, characterized by decreased lesion severity, parasite burden and enhanced Th1 responses. Results warrant further development of carbohydrate-based VLP vaccine as a potential approach against leishmaniasis. Studies will investigate antigen presentation optimization, the longevity of the immunity, and induction of cross-protection against Leishmania species. Funding Source n/a Topic Categories Vaccines and Immunotherapy (VAC)