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

• Published in: Biomedicine & pharmacotherapy 2020-06, Vol.126, p.110097-110097, Article 110097
• Main Authors: Bastos, Daniel Silva Sena, Miranda, Bianca Meirelles, Fialho Martins, Thais Viana, Guimarães Ervilha, Luiz Otávio, Souza, Ana Cláudia Ferreira, de Oliveira Emerick, Sabrina, Carneiro da Silva, Adriana, Novaes, Rômulo Dias, Neves, Mariana Machado, Santos, Eliziária Cardoso, de Oliveira, Leandro Licursi, Marques-da-Silva, Eduardo de Almeida
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan; Antioxidants; Disease Models, Animal; Glycosphingolipids - immunology; Immunization; Leishmania infantum - immunology; Leishmaniasis - parasitology; Leishmaniasis - pathology; Leishmaniasis - prevention & control; Liver Diseases, Parasitic - parasitology; Liver Diseases, Parasitic - pathology; Liver Diseases, Parasitic - prevention & control; Liver morphology; LPG3; Mice; Oxidative Stress; Parasite Load; Protozoan Vaccines - immunology; Reactive Nitrogen Species - metabolism; Reactive Oxygen Species - metabolism; Recombinant Proteins - immunology; Vaccine; Visceral leishmaniasis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110097

[Display omitted] •Vaccine using rLPG3 in mice improves the liver enzymatic antioxidant defenses.•rLPG3 + SAP vaccine preserves hepatic architecture and reduces granuloma formation in L. infantum chagasi infection.•rLPG3 + SAP vaccine reduces the hepatic parasitism in 99 % in mice infected with L. infantum chagasi. 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. 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. 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. 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.