Nano DNA Vaccine Encoding Toxoplasma gondii Histone Deacetylase SIR2 Enhanced Protective Immunity in Mice.

Zhengqing Yu,Jianxun Luo,Lixin Xu,Junlong Liu,Xiaokai Song,Wandi Cao,Ruofeng Yan,Xiangrui Li,Muhammad Tahir Aleem,Yujia Lu

doi:10.3390/pharmaceutics13101582

Abstract

The pathogen of toxoplasmosis, Toxoplasma gondii (T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encoding T. gondii histone deacetylase SIR2 (pVAX1-SIR2) was constructed. To enhance the efficacy, chitosan and poly (d, l-lactic-co-glycolic)-acid (PLGA) were employed to design nanospheres loaded with the DNA vaccine, denoted as pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres. The pVAX1-SIR2 plasmids were transfected into HEK 293-T cells, and the expression was evaluated by a laser scanning confocal microscopy. Then, the immune protections of pVAX1-SIR2 plasmid, pVAX1-SIR2/CS nanospheres, and pVAX1-SIR2/PLGA nanospheres were evaluated in a laboratory animal model. The in vivo findings indicated that pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres could generate a mixed Th1/Th2 immune response, as indicated by the regulated production of antibodies and cytokines, the enhanced maturation and major histocompatibility complex (MHC) expression of dendritic cells (DCs), the induced splenocyte proliferation, and the increased percentages of CD4+ and CD8+ T lymphocytes. Furthermore, this enhanced immunity could obviously reduce the parasite burden in immunized animals through a lethal dose of T. gondii RH strain challenge. All these results propose that pVAX1-SIR2 plasmids entrapped in chitosan or PLGA nanospheres could be the promising vaccines against acute T. gondii infections and deserve further investigations.

Highlights

Introduction published maps and institutional affilToxoplasma gondii (T. gondii) is an obligate intracellular parasite distributed worldwide and infect a vast array of warm-blooded vertebrates including humans [1,2]
The plasmid sequencing analysis revealed the insert were the open reading frame (ORF) of T. gondii SIR2 gene. All these results indicated that the pVAX1-SIR2 plasmid was correctly constructed
The results suggested that PLGA and chitosan nanospheres were effective at fective at DNA vaccine delivery and anti-plasmid biodegradation, and they were safe to DNA vaccine delivery and anti-plasmid biodegradation, and they were safe to the animals

Summary

Introduction

Introduction published maps and institutional affilToxoplasma gondii (T. gondii) is an obligate intracellular parasite distributed worldwide and infect a vast array of warm-blooded vertebrates including humans [1,2].

Methods

Results

Discussion

Conclusion