Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 16, Issue -, Pages 7153-7168Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S315786
Keywords
Schistosoma mansoni; vaccine; TSP-2 antigen; outer membrane vesicles; OMV; biotin-avidin coupling; nanoparticle
Funding
- FAPESP [2017/24632-6]
- Fundacao Butantan
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Brazil (CAPES) [001]
- Conselho Nacional de Desenvolvimento Cientifico e Pesquisa (CNPq) [160861/2017-9]
- Italy-Brazil Joint Laboratories initiative of the CNR
- Servico de Microscopia Eletronica from FIOCRUZ/BA
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The coupling of the SmTSP-2 antigen with OMVs significantly enhances the immunogenicity of the vaccine in mice, indicating the potential effectiveness of this platform in novel vaccine strategies.
Purpose: The use of adjuvants can significantly strengthen a vaccine's efficacy. We sought to explore the immunization efficacy of bacterial outer membrane vesicles (OMVs) displaying the Schistosoma mansoni antigen, SmTSP-2, through a biotin-rhizavidin coupling approach. The rationale is to exploit the nanoparticulate structure and the adjuvant properties of OMVs to induce a robust antigen-specific immune response, in light of developing new vaccines against S. mansoni. Materials and Methods: OMVs were obtained from Neisseria lactamica and conjugated with biotin. The recombinant SmTSP-2 in fusion with the biotin-binding protein rhizavidin (rRzvSmTSP-2) was produced in E. coli and coupled to biotinylated OMVs to generate an OMV complex displaying SmTSP-2 on the membrane surface (OMV:rSmTSP-2). Transmission electron microscopy (TEM) and dynamic light scattering analysis were used to determine particle charge and size. The immunogenicity of the vaccine complex was evaluated in C57BL/6 mice. Results: The rRzvSmTSP-2 protein was successfully coupled to biotinylated OMVs and purified by size-exclusion chromatography. The OMV:rSmTSP-2 nanoparticles showed an average size of 200 nm, with zeta potential around - 28 mV. Mouse Bone Marrow Dendritic Cells were activated by the nanoparticles as determined by increased expression of the co stimulatory molecules CD40 and CD86, and the proinflammatory cytokines (TNF-alpha, IL-6 and IL-12) or IL-10. Splenocytes of mice immunized with OMV:rSmTSP-2 nanoparticles reacted to an in vitro challenge with SmTSP-2 with an increased production of IL-6, IL-10 and IL-17 and displayed a higher number of CD4+ and CD8+ T lymphocytes expressing IFN-gamma, IL-4 and IL-2, compared to mice immunized with the antigen alone. Immunization of mice with OMV:rSmTSP-2 induced a 100-fold increase in specific anti-SmTSP-2 IgG antibody titers, as compared to the group receiving the recombinant rSmTSP-2 protein alone or even co-administered with unconjugated OMV. Conclusion: Our results demonstrate that the SmTSP-2 antigen coupled with OMVs is highly immunogenic in mice, supporting the potential effectiveness of this platform for improved antigen delivery in novel vaccine strategies.
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