Immunogenicity of trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against EV-A71 and CV-A16

Aim: To develop a trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against hand foot and mouth disease (HFMD) and assess its immunogenicity in mice.
Materials & methods: Trivalent plasmid carrying the VP1 and VP2 genes of EV-A71, VP1 gene of CV-A16 was encapsulated in Chitosan-TPP nanoparticles through ionic gelation. In vitro characterization and in vivo immunization studies of the CS-TPP-NPs (pIRES-VP121) were performed.
Results: Mice administered with CS-TPP NPs (pIRES-VP121) intramuscularly were observed to have the highest IFN-γ response. Sera from mice immunized with the naked pDNA and CS-TPP-NPs (pIRES-VP121) demonstrated good viral clearance against wild-type EV-A71 and CV-A16 in RD cells.
Conclusion: CS-TPP-NPs (pIRES-VP121) could serve as a prototype for future development of multivalent HFMD DNA vaccine candidates.
Currently, there are no US-FDA approved vaccine against HFMD. China-FDA approved monovalent HFMD inactivated vaccines were unable to provide cross protection against other enterovirus serotypes.
We have developed a trivalent plasmid vaccine candidate, pIRES-VP121 which encodes the VP1 and VP2 genes of EV-A71 and the VP1 gene of CV-A16.
We successfully synthesized Chitosan TPP nanoparticles encapsulating DNA Encapsulation of plasmid vaccine candidate pIRES-VP121 through ionic gelation, yielding highly monodisperse nanoparticles with CS-TPP-NPs (pIRES-VP121) with >70% encapsulation efficiency.
Encapsulation of plasmid vaccine candidate pIRES-VP121 through ionic gelation successfully formulated sub-200 nm, spherical shaped, mildly cationic (+10 mV) and highly monodisperse CS-TPP-NPs (pIRES-VP121) with >70% encapsulation efficiency.
Chitosan NPs encapsulations improved T cell immunogenicity resulting in higher IFN-γ expressing CD4+/CD8+ T cells population and IFN-γ secretion compared with mice immunized with naked pIRES-VP121.
Enhanced B cell neutralizing efficacy were demonstrated by mice sera (1:16 dilution) immunized with CS-TPP-NPs (pIRES-VP121) against the wild-type EV-A71 B4 and CV-A16/N132 strain enteroviruses in comparison with naked pIRES-VP121 immunization.
These findings showed the potential of a trivalent DNA plasmid to serve as a prototype for future development of multivalent DNA vaccine candidate against HFMD.