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Sustainable Development Goals
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ROBUST IMMUNE RESPONSE INDUCED BY SCHISTOSOMA MANSONI TSP-2 ANTIGEN COUPLED TO BACTERIAL OUTER MEMBRANE VESICLES
Vacina
Antígeno TSP
Vesículas de membrana
Acoplamento
Nanopartícula
Vaccine
TSP-2 antigen
Outer membrane vesicles
OMV
Biotin-avidin coupling
Nanoparticle
Author
Barbosa, Mayra M F
Kanno, Alex I
Barazzone, Giovana C
Rodriguez, Dunia
Pancakova, Violeta
Trentini, Monalisa
Mauro, Eliana L Faquim
Freitas, Amanda P
Khouri, Mariana I
Silva, Jessica Lobo
Goncalves, Viviane M
Schenkman, Rocilda P F
Tanizaki, Martha M
Boraschi, Diana
Malley, Richard
Farias, Leonardo P
Leite, Luciana C C
Kanno, Alex I
Barazzone, Giovana C
Rodriguez, Dunia
Pancakova, Violeta
Trentini, Monalisa
Mauro, Eliana L Faquim
Freitas, Amanda P
Khouri, Mariana I
Silva, Jessica Lobo
Goncalves, Viviane M
Schenkman, Rocilda P F
Tanizaki, Martha M
Boraschi, Diana
Malley, Richard
Farias, Leonardo P
Leite, Luciana C C
Affilliation
"Múltipla ver em Notas"
Abstract
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 costimulatory
molecules CD40 and CD86, and the proinflammatory cytokines (TNF-α, 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-γ, 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.
Keywords in Portuguese
Schistosoma mansoniVacina
Antígeno TSP
Vesículas de membrana
Acoplamento
Nanopartícula
Keywords
Schistosoma mansoniVaccine
TSP-2 antigen
Outer membrane vesicles
OMV
Biotin-avidin coupling
Nanoparticle
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