In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

Chamakh-Ayari, Rym; Bras-Gonçalves, Rachel; Bahi-Jaber, Nargès; Petitdidier, Elodie; Markikou-Ouni, Wafa; Karim, Abdul; Moreno, Javier; Carrillo, Eugenia; Salotra, Poonam; Kaushal, Himanshu; Negi, Narender Singh; Arévalo, Jorge; Falconi-Agapito, Francesca; Privat, Angela; Cruz, María; Pagniez, Julie; Papierok, Gérard; Rhouma, Faten Bel Haj; Torres, Pilar; Lemesre, Jean-Loup; Chenik, Mehdi; Meddeb-Garnaoui, Amel

doi:10.1371/journal.pone.0092708

Cited by 38 publications

(36 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various factors can influence immunogenicity of a protein such as differences in amino acid sequences, immunogenic dominant epitopes, individual-related factors including immune status and genetic features. Similarly, to these results, we have recently demonstrated that LaPSA-38S, a L. amazonensis promastigote surface antigen, induced high specific IFN-γ levels in individuals immune to L. major and L. infantum infection [24]. Our previous data and those of other authors have shown Leishmania protein-specific IFN-γ levels, in immune individuals [25–27].…”

Section: Discussionsupporting

confidence: 83%

Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundWe previously identified a Leishmania (L.) major large RAB GTPase (LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania species while displaying low level of homology with mammalian homologues. Leishmania small RAB GTPases proteins have been involved in regulation of exocytic and endocytic pathways whereas the role of large RAB GTPases proteins has not been characterized yet. We report here the immunogenicity of both recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major or L. infantum.MethodsPBMC were isolated from individuals cured of L. major (CCLm) or from healthy individuals. The latter were subdivided into high or low IFN-γ responders. Healthy high IFN-γ responders, considered as asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum (HHRLi). Healthy low IFN-γ responders (HLR) were considered as naïve controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC. Cytokines were analysed by CBA and ELISA and phenotypes of IFN-γ-producing cells were analysed by flow cytometry.ResultsBoth rLmlRAB and rLmlRABC induced high significant levels of IFN-γ in CCLm, HHRLm and HHRLi groups. Phenotype analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a significant increase in the percentage of specific IFN-γ-producing CD4+ and CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm. Low but significant granzyme B levels were detected in naïve group. IL-10 was detected in immune and naïve individuals.ConclusionWe showed that rLmlRAB protein and its divergent carboxy-terminal part induced a predominant Th1 response in individuals immune to L. major or L. infantum. Our results suggest that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates against cutaneous and visceral leishmaniasis.

show abstract

Section: Discussionsupporting

confidence: 83%

Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the present study, we observed a significantly high percentage of both CD8 + CD69 + and CD4 + CD69 + T cells in the PKDL group. This is similar to the observation in individuals with VL history but distinct from cured CL individuals, where a high level of CD4 + CD69 + T cells was demonstrated to be responsible for the cellular immunity to L. major infection . Taken together, the elevated levels of both activated CD4 + and CD8 + T cells, coupled with high secretion of granzyme B upon in‐vitro TSLA stimulation, suggests the role of cytotoxic activity in providing resistance against L. donovani infection in PKDL.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India

Kaushal

Bras-Gonçalves

Avishek

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryPost-kala-azar dermal leishmaniasis (PKDL) is a chronic dermal complication that occurs usually after recovery from visceral leishmaniasis (VL). The disease manifests into macular, papular and/or nodular clinical types with mono-or polymorphic presentations. Here, we investigated differences in immunological response between these two distinct clinical forms in Indian PKDL patients. Peripheral blood mononuclear cells of PKDL and naive individuals were exposed in vitro to total soluble Leishmania antigen (TSLA). The proliferation index was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based lymphoproliferative assay. Cytokines and granzyme B levels were determined by cytometric bead array. Parasite load in tissue biopsy samples of PKDL was quantified by quantitative polymerase chain reaction (qPCR). The proportion of different lymphoid subsets in peripheral blood and the activated T cell population were estimated using flow cytometry. The study demonstrated heightened cellular immune responses in the polymorphic PKDL group compared to the naive group. The polymorphic group showed significantly higher lymphoproliferation, increased cytokines and granzyme B levels upon TSLA stimulation, and a raised proportion of circulating natural killer (NK) T cells against naive controls. Furthermore, the polymorphic group showed a significantly elevated proportion of activated CD4 1 and CD8 1 T cells upon in-vitro TSLA stimulation. Thus, the polymorphic variants showed pronounced cellular immunity while the monomorphic form demonstrated a comparatively lower cellular response. Additionally, the elevated level of both activated CD4 1 and CD8 1 T cells, coupled with high granzyme B secretion upon in-vitro TSLA stimulation, indicated the role of cytotoxic cells in resistance to L. donovani infection in polymorphic PKDL.

show abstract

“…Leishmania-specific antibodies were determined by ELISA as reported earlier. 29,30 Briefly, 96-well polystyrene flatbottom ELISA plates (NUNC MaxiSorp ™ , Brandby, Denmark) were coated with 100 μL of TSLA (10 μg/mL) in bicarbonate buffer (pH 9.0) overnight at 4°C. The plates were washed and blocked with 1% bovine serum albumin for 2 hours at 37°C and washed thrice with phosphate-buffered saline containing 0.1% Tween 20 (PBST).…”

Section: Methodsmentioning

confidence: 99%

Serological and Molecular Analysis of Leishmania Infection in Healthy Individuals from Two Districts of West Bengal, India, Endemic for Visceral Leishmaniasis

Kaushal

Bhattacharya

Verma

et al. 2017

The American Society of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Several epidemiological studies have indicated the presence of asymptomatic infections with in the Indian subcontinent, where parasite transmission is considered anthroponotic. In India, such asymptomatic cases have been identified in the state of Bihar. We explored here, the presence of asymptomatic infection among healthy individuals living in two districts in the state of West Bengal, India, using serological and molecular tests. Blood samples of 246 healthy individuals were collected from nine villages of Malda and Murshidabad districts in West Bengal, considered endemic for visceral leishmaniasis (VL). Real-time quantitative polymerase chain reaction (qPCR) was performed for the quantification of parasite load in the blood. In addition, two serological tests were carried out to demonstrate anti- antibodies: rK39 strip test and anti-total soluble antigen IgG using enzyme-linked immunosorbent assay method. Nearly one-fifth (53/246) of the screened population was positive in qPCR as against 10.97% (27/246) positive in rK39 strip test. A range of parasite load was observed in the blood of identified asymptomatic cases with a median value of 7.7 parasites/mL (range = 1-65). There was poor agreement between qPCR and serological tests (κ = 0.089, = 0.13), and 29.62% and 20.54% of the population were qPCR positive in seropositive and seronegative groups, respectively. Combined molecular and serological tests enhanced the capacity to detect asymptomatic infection in healthy individuals residing in the endemic areas of VL. A significant proportion of asymptomatic individuals was detected in the examined endemic regions of West Bengal that might play a role in promoting VL transmission.

show abstract

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

Cited by 38 publications

References 63 publications

Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis

Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis

Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India

Serological and Molecular Analysis of Leishmania Infection in Healthy Individuals from Two Districts of West Bengal, India, Endemic for Visceral Leishmaniasis

Contact Info

Product

Resources

About