ABSTRACT
Toxoplasma gondii is an obligate intracellular parasite that can infect a variety of mammals including humans and causes toxoplasmosis. Unfortunately, a protective and safe vaccine against toxoplasmosis hasn't been developed yet. In this study, we developed a DNA vaccine encoding the SRS13 protein and immunized BALB/c mice thrice with pVAX1-SRS13 through the intramuscular route (IM) or intradermally using an electroporation device (ID + EP). The immunogenicity of pVAX1-SRS13 was analyzed by ELISA, Western blot, cytokine ELISA, and flow cytometry. The protective efficacy of the pVAX1-SRS13 was investigated by challenging mice orally with T. gondii PRU strain tissue cysts. The results revealed that pVAX1-SRS13 administered through IM or ID + EP routes induced high level of anti-SRS13 IgG antibody responses (P = 0.0037 and P < 0.0001). The IFN-γ level elicited by the pVAX1-SRS13 (ID + EP) was significantly higher compared to the control group (P = 0.00159). In mice administered with pVAX1-SRS13 (ID + EP), CD8+ cells secreting IFN-γ was significantly higher compared to pVAX1-SRS13 (IM) (P = 0.0035) and the control group (P = 0.0068). Mice vaccinated with the SRS13 DNA vaccine did not induce significant IL-4 level. Moreover, a significant reduction in the number of tissue cysts and the load of T. gondii DNA was detected in brains of mice administered with pVAX1-SRS13 through ID + EP and IM routes compared to controls. In conclusion, the SRS13 DNA vaccine was found to be highly immunogenic and confers strong protection against chronic toxoplasmosis.
Subject(s)
Antibodies, Protozoan , Electroporation , Mice, Inbred BALB C , Protozoan Proteins , Protozoan Vaccines , Toxoplasma , Vaccines, DNA , Vaccines, DNA/immunology , Vaccines, DNA/administration & dosage , Animals , Toxoplasma/immunology , Toxoplasma/genetics , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Electroporation/methods , Protozoan Vaccines/immunology , Protozoan Vaccines/administration & dosage , Protozoan Proteins/immunology , Protozoan Proteins/genetics , Mice , Female , Toxoplasmosis, Animal/prevention & control , Toxoplasmosis, Animal/immunology , Immunoglobulin G/blood , Toxoplasmosis/prevention & control , Toxoplasmosis/immunology , Antigens, Protozoan/immunology , Antigens, Protozoan/genetics , Interferon-gamma/immunology , CD8-Positive T-Lymphocytes/immunologyABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive lethal diseases among other cancer types. Gut microbiome and its metabolic regulation play a crucial role in PDAC. Metabolic regulation in the gut is a complex process that involves microbiome and microbiome-derived short-chain fatty acids (SCFAs). SCFAs regulate inflammation, as well as lipid and glucose metabolism, through different pathways. This review aims to summarize recent developments in PDAC in the context of gut and oral microbiota and their associations with short-chain fatty acid (SCFA). In addition to this, we discuss possible therapeutic applications using microbiota in PDAC.