Haptens in visceral leishmaniasis. Development of solid phase assays for diagnosis and its immunology in experimental models.

• Grant number: 17/26558-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2018
• End date: June 30, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Heitor Franco de Andrade Junior
• Grantee: Heitor Franco de Andrade Junior
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Camila Aparecida de Carvalho

Abstract

Visceral leishmaniasis (VL) is an epidemic in Brazil, and its diagnosis and immunology have been studied using classical or protein antigens in general. Haptens are macromolecules of molecular weight between 1 and 5 KDa which are composed of peptides, small polysaccharides and complex lipids, and which have the ability to react with antibodies and immune cells incompletely, perhaps interfering with the immune response. Several chronic human diseases occur with high levels of antibodies, but the most common is VL. Molecular exclusion chromatography methods allow the separation of these molecules from crude extracts of promastigotes, allowing their purification and characterization, as well as their association with carrier molecules and thus use in classical assays. In this project, we intend to study the biochemistry and immunology of haptens from crude extracts of promastigotes and axenic amastigotes of L. (L.) infantum chagasi by sequential molecular exclusion chromatography. This involves: quantification by dosing of sugars; b: structural studies by MALDI-TOF and mass spectrometry; c: identification and quantification of these haptens in urine or blood of experimental models; d: determination of specific antibodies by solid phase antibody capture assays or with hybrids thereof with carrier proteins in experimental models of hamsters or of genetically deficient BALB / C ³-interferon mice; e: studies of its effects on the immune response in these models, through in vivo and in vitro studies. This will allow to determine if these haptens interfere with the immune response in VL in immunosuppression and visceral disease and, therefore, with clinical and pathogenetic importance. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE CARVALHO, CAMILA APARECIDA; FERRAO, THIAGO FIDELIS; NOVAIS DE FREITAS, FLAVIA REGINA; DE ANDRADE JUNIOR, HEITOR FRANCO. High levels of serum glycans monovalent IgG immune complexes detected by dissociative ELISA in experimental visceral leishmaniasis. IMMUNOLOGY, v. 158, n. 4, p. 314-321, DEC 2019. (17/26558-9, 13/50218-2)

DE CARVALHO, CAMILA APARECIDA; FERRAO, THIAGO FIDELIS; CAVALCANTE, FERNANDA SIQUEIRA; NOVAIS DE FREITAS, FLAVIA REGINA; MEIRELES, LUCIANA REGINA; DE ANDRADE JUNIOR, HEITOR FRANCO. Early high avidity specific IgG production in experimental hamster visceral leishmaniasis. Parasitology Research, v. 119, n. 11, AUG 2020. (17/26558-9, 17/14675-0)

APARECIDA DE CARVALHO, CAMILA; MITSUYOSHI HIRAMOTO, ROBERTO; REGINA MEIRELES, LUCIANA; FRANCO DE ANDRADE JUNIOR, HEITOR. Serum antibodies blocked by glycan antigens in canine visceral leishmaniasis serology are mostly IgA immune complexes. Parasitology, v. 148, n. 12, p. 1509-1515, OCT 2021. (17/14675-0, 17/26558-9)