Lipophosphoglycan-3 recombinant protein vaccine controls hepatic parasitism and prevents tissue damage in mice infected by Leishmania infantum chagasi

Abstract

Aims: In this work, we aimed to evaluate the effects of the Leishmania infantum chagasi infection on the liver of vaccinated mice, considering parameters of tissue damage and the inflammatory response elicited by vaccination. Main methods: We used recombinant LPG3 protein (rLPG3) as immunogen in BALB/c mice before challenge with promastigote forms of L. infantum chagasi. The animals were separated into five groups: NI: non-infected animals; NV: non-vaccinated; SAP: treated with saponin; rLPG3: immunized with rLPG3; rLPG3 + SAP: immunized with rLPG3 plus SAP. The experiment was conducted in replicate, and the vaccination protocol consisted of three subcutaneous doses of rLPG3 (40 μg + two boosters of 20 μg). The mice were challenged two weeks after the last immunization. Key findings: Our results showed that rLPG3 + SAP immunization decreased the parasite burden in 99 %, conferring immunological protection in the liver of the infected animals. Moreover, the immunization improved the antioxidant defenses, increasing CAT and GST activity, while reducing the levels of oxidative stress markers, such as H2O2 and NO3/NO2, and carbonyl protein in the organ. As a consequence, rLPG3 + SAP immunization preserved tissue integrity and reduced the granuloma formation, inflammatory infiltrate and serum levels of AST, ALT, and ALP. Significance: Taken together, these results showed that rLPG3 vaccine confers liver protection against L. infantum chagasi in mice, while maintaining the liver tissue protected against the harmful inflammatory effects caused by the vaccine followed by the infection.

Keywords

• LPG3
• Visceral leishmaniasis
• Liver morphology
• Oxidative stress
• Vaccine