Immunodominant Antigens of Leishmania chagasi Associated with Protection against Human Visceral Leishmaniasis

Abstract

Background Protection and recovery from visceral leishmaniasis (VL) have been associated with cell-mediated immune (CMI) responses, whereas no protective role has been attributed to humoral responses against specific parasitic antigens. In this report, we compared carefully selected groups of individuals with distinct responses to Leishmania chagasi to explore antigen-recognizing IgG present in resistant individuals. Methodology and Principal Findings VL patients with negative delayed-type hypersensitivity (DTH) were classified into the susceptible group. Individuals who had recovered from VL and converted to a DTH+ response, as well as asymptomatic infected individuals (DTH+), were categorized into the resistant group. Sera from these groups were used to detect antigens from L. chagasi by conventional and 2D Western blot assays. Despite an overall reduction in the reactivity of several proteins after DTH conversion, a specific group of proteins (approximately 110–130 kDa) consistently reacted with sera from DTH converters. Other antigens that specifically reacted with sera from DTH+ individuals were isolated and tandem mass spectrometry followed by database query with the protein search engine MASCO were used to identify antigens. The serological properties of recombinant version of the selected antigens were tested by ELISA. Sera from asymptomatic infected people (DTH+) reacted more strongly with a mixture of selected recombinant antigens than with total soluble Leishmania antigen (SLA), with less cross-reactivity against Chagas disease patients' sera. Significance Our results are the first evidence of leishmania proteins that are specifically recognized by sera from individuals who are putatively resistant to VL. In addition, these data highlight the possibility of using specific proteins in serological tests for the identification of asymptomatic infected individuals.

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

“…Similar results were reported in studies determining the CMI at endemic areas for L. infantum and L. donovani [21]. This suggests that many immunodominant antigens are shared across the species and a global assay could be developed [40].…”

Identification of Immunoreactive Leishmania infantum Protein Antigens to Asymptomatic Dog Sera through Combined Immunoproteomics and Bioinformatics Analysis

“…chagasi or L . donovani parasites, etiological agents of ZVL in South America and anthroponotic VL in India, respectively [ 15 , 44 , 45 , 46 ]. The current study offers complementary findings, since it is the first to investigate the immunoreactive proteome of L .…”

“…In asymptomatic CVL, humoral responses although not correlated directly with protection, are largely T-cell dependent [ 28 , 46 ]. Consequently, antigens that react with antibodies in asymptomatic animal sera may be associated with protective immune responses and may represent potential vaccine candidates.…”

Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice

“…braziliensis ( Fig 1 ), as occur with other intracellular parasite proteins families. The presence of antibodies against intracellular proteins in sera samples from patients of CL an ML, as well as in cured VL patients, reflects the strong antigenicity of these families [ 30 , 31 , 42 ]. Some variability in the recognition of the individual LiPABPs was observed among sera samples from different patients.…”

“…Human serum samples were obtained from clinical and parasitologically diagnosed patients. For the present study, anonymized samples were randomly selected from a sera bank (LIP-CPqGM-FIOCRUZ) built for previous independent studies conducted in Brazil in endemic areas for ML [ 30 ] or VL [ 31 ]. Canine symptomatic VL sera from L .…”