With Chitosan and PLGA as the Delivery Vehicle, Toxoplasma gondii Oxidoreductase-Based DNA Vaccines Decrease Parasite
Zhengqing Yu1, Wandi Cao1, Xuchen Gao1
1Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Frontiers in Immunology
|September 13, 2021
Summary
A new DNA vaccine using chitosan or PLGA nanospheres effectively targets Toxoplasma gondii oxidoreductase. This promising vaccine candidate significantly reduces parasite burden in mice with acute toxoplasmosis.
Area of Science:
- Immunology
- Parasitology
- Vaccine Development
Background:
- Toxoplasma gondii (T. gondii) poses a significant public health threat, yet effective preventive or therapeutic strategies are lacking.
- Current limitations necessitate the development of novel approaches to combat toxoplasmosis in humans and animals.
Purpose of the Study:
- To develop and evaluate a DNA vaccine encoding T. gondii oxidoreductase from the short-chain dehydrogenase/reductase family (TgSDRO-pVAX1).
- To enhance vaccine efficacy by encapsulating TgSDRO-pVAX1 within chitosan (CS) and poly lactic-co-glycolic acid (PLGA) nanospheres.
- To assess the immunogenicity and protective efficacy of the developed nanosphere-based DNA vaccines against acute toxoplasmosis.
Main Methods:
- Construction of a DNA vaccine (TgSDRO-pVAX1) and its encapsulation into CS and PLGA nanospheres.
- In vitro characterization of nanospheres, including plasmid loading, stable release, transfection efficiency (HEK 293-T cells), western blotting, and laser confocal microscopy.
- In vivo assessment in a mouse model of acute toxoplasmosis, evaluating Th1/Th2 cellular and humoral immunity, antibody and cytokine secretion, dendritic cell maturation, T lymphocyte populations (CD4+, CD8+), and parasite burden.
Main Results:
- TgSDRO-pVAX1 successfully encapsulated in CS and PLGA nanospheres demonstrated stable plasmid release and effective transfection.
- Immunization induced robust Th1/Th2 immune responses, modulated antibody and cytokine profiles, promoted dendritic cell maturation, and increased CD4+ and CD8+ T lymphocyte percentages.
- Both TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres significantly reduced parasite burden in mice, indicating substantial protection against acute toxoplasmosis.
Conclusions:
- The TgSDRO-pVAX1 DNA vaccine, delivered via chitosan or PLGA nanospheres, represents a promising vaccine candidate against acute toxoplasmosis.
- Chitosan and PLGA nanospheres serve as effective and interchangeable delivery vehicles, enhancing the immunogenicity and protective efficacy of the DNA vaccine.
- This study provides a viable strategy for developing novel vaccines against T. gondii infections.
