Articolo in rivista, 2021, ENG, 10.2147/IJN.S315786

Robust Immune Response Induced by Schistosoma mansoni TSP-2 Antigen Coupled to Bacterial Outer Membrane Vesicles

Barbosa, Mayra M. F.; Kanno, Alex, I; Barazzone, Giovana C.; Rodriguez, Dunia; Pancakova, Violeta; Trentini, Monalisa; Faquim-Mauro, Eliana L.; Freitas, Amanda P.; Khouri, Mariana, I; Lobo-Silva, Jessica; Goncalves, Viviane M.; Schenkman, Rocilda P. F.; Tanizaki, Martha M.; Boraschi, Diana; Malley, Richard; Farias, Leonardo P.; Leite, Luciana C. C.

Inst Butantan; Univ Sao Paulo; Univ Claude Bernard Lyon 1 UCBL1; Inst Butantan; Fundacao Oswaldo Cruz; CNR; Stn Zool Anton Dohrn; Chinese Acad Sci; Boston Childrens Hosp

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.

International journal of nanomedicine (Online) 16 , pp. 7153–7168

Keywords

Schistosoma mansoni, vaccine, TSP-2 antigen, outer membrane vesicles, OMV, biotin-avidin coupling, nanoparticle

CNR authors

Boraschi Diana

CNR institutes

ID: 463449

Year: 2021

Type: Articolo in rivista

Creation: 2022-02-01 10:43:34.000

Last update: 2022-02-01 10:43:34.000

CNR authors

External links

OAI-PMH: Dublin Core

OAI-PMH: Mods

OAI-PMH: RDF

DOI: 10.2147/IJN.S315786

External IDs

CNR OAI-PMH: oai:it.cnr:prodotti:463449

DOI: 10.2147/IJN.S315786

ISI Web of Science (WOS): 000711150400003