Contrasting human cytokine responses to promastigote whole-cell extract and the Leishmania analogue receptor for activated C kinase antigen of L. amazonensis in natural infection versus immunization

Azeredo-Coutinho, Rilza Beatriz; Matos, Denise C. S.; Armôa, G. G. R.; Maia, Rouselaine Marinho; Schubach, Armando; Mayrink, Wilson; Mendonça, Sergio C. F.

doi:10.1111/j.1365-2249.2008.03705.x

Cited by 12 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The IL-10 production by PBMC from hCL as well as healthy individuals might be due to the high level of conservation of MAPKK proteins in eukaryotic species. Although MAPKK stimulates high IL-10 levels, it could constitute a potential vaccine candidate since it was recently reported that the human immune response to crude and defined Leishmania antigens generated during immunization can differ from that induced by natural infection (1). Similarly, MAPKK used as a vaccine might induce a dominant Th1 response compatible with protection.…”

mentioning

confidence: 99%

Cellular and Humoral Responses toLeishmania majorVirulence Factors in Healed Cutaneous Leishmaniasis and Mediterranean Visceral Leishmaniasis Patients

Lakhal-Naouar

Boussoffara

Meddeb-Garnaoui

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

Cellular and humoral immune responses of healed cutaneous leishmaniasis and Mediterranean visceral leishmaniasis patients were evaluated against results for Leishmania major virulence proteins L. major protein disulfide isomerase (LmPDI) and mitogen-activated protein kinase kinase (MAPKK). Only MAPKK induces significant peripheral blood mononuclear cell proliferation with gamma interferon production as well as antibody responses. Thus, MAPKK may be of interest in Leishmania vaccination and serodiagnosis.The leishmaniases are diseases caused by vector-borne pathogens that represent a major public health problem affecting the lives of millions of people worldwide (http://www.who .int/whr/en). Depending on the parasite species and on the immunological response of the human host, leishmaniasis ranges from an asymptomatic infection to a self-limiting cutaneous lesion(s) or a fatal visceral form.No anti-Leishmania vaccine is available at the moment. Different studies showed that development of Th1-and Leishmania-specific cytotoxic immune responses correlate with healing of patients with cutaneous leishmaniasis (CL) (3,12). An intense effort is being made to identify antigens that could induce an immune state similar to that developed by individuals who recover from symptomatic infection and are resistant to a subsequent natural challenge. Such antigens may contribute to the development of an anti-Leishmania vaccine.Diagnostic tools targeting leishmaniasis are available. However, parasite detection is invasive and poorly sensitive. Serological diagnosis using various techniques based on detection of Leishmania-specific antibodies that are developed during acute disease are often more sensitive, less time-consuming, and more user friendly (4,11,15).In an attempt to identify new antigens to be used as vaccines or for serodiagnosis, we focused on Leishmania virulence factors. Indeed, several studies described these factors as potentially immunogenic in humans, mice, and, more recently, dogs (6,8,9,13). Here, cellular and humoral immune responses of healed CL (hCL) and Mediterranean visceral leishmaniasis (MVL) patients were evaluated against results for Leishmania major protein disulfide isomerase (LmPDI) and mitogen-activated protein kinase kinase (MAPKK), which we and others previously described as potential virulence factors (2, 10).We produced LmPDI (55 kDa) and MAPKK (40 kDa) in the prokaryotic expression pET system (Novagen, Gibbstown, NJ) and then purified them by affinity chromatography (Fig. 1). Lymphoproliferative responses (Fig. 2) and gamma interferon (IFN-␥) and interleukin-10 (IL-10) production (Fig. 3) induced by recombinant LmPDI and MAPKK (10 g/ml) were characterized in vitro using peripheral blood mononuclear cells (PBMC) from two groups. The first group consisted of 18 hCL patients (age range, 17 to 42 years; mean Ϯ standard deviation [SD], 28 Ϯ 10.9 years) living in an area of L. major infection endemicity (the governorate of Sidi Bouzid, Tunisia). Diagnosis of leishmaniasis was based on the presence o...

show abstract

mentioning

confidence: 99%

Cellular and Humoral Responses toLeishmania majorVirulence Factors in Healed Cutaneous Leishmaniasis and Mediterranean Visceral Leishmaniasis Patients

Lakhal-Naouar

Boussoffara

Meddeb-Garnaoui

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Both the whole-cell extract of leishmania promastigotes and its supernatant have been indistinctly used as antigenic material in in vitro tests and as pre-clinical and clinical vaccine candidates [ 35 – 37 ]. Besides, it has been observed that detergent-solubilized proteins of a crude extract of L .…”

Section: Resultsmentioning

confidence: 99%

“…amazonensis and L . braziliensis promastigotes was reported to be more antigenic than the supernatant [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

Ultradeformable Archaeosomes for Needle Free Nanovaccination with Leishmania braziliensis Antigens

et al. 2016

View full text Add to dashboard Cite

Total antigens from Leishmania braziliensis promastigotes, solubilized with sodium cholate (dsLp), were formulated within ultradeformable nanovesicles (dsLp-ultradeformable archaeosomes, (dsLp-UDA), and dsLp-ultradeformable liposomes (dsLp-UDL)) and topically administered to Balb/c mice. Ultradeformable nanovesicles can penetrate the intact stratum corneum up to the viable epidermis, with no aid of classical permeation enhancers that can damage the barrier function of the skin. Briefly, 100 nm unilamellar dsLp-UDA (soybean phosphatidylcholine: Halorubrum tebenquichense total polar lipids (TPL): sodium cholate, 3:3:1 w:w) of -31.45 mV Z potential, containing 4.84 ± 0.53% w/w protein/lipid dsLp, 235 KPa Young modulus were prepared. In vitro, dsLp-UDA was extensively taken up by J774A1 and bone marrow derive cells, and the only that induced an immediate secretion of IL-6, IL-12p40 and TNF-α, followed by IL-1β, by J774A1 cells. Such extensive uptake is a key feature of UDA ascribed to the highly negatively charged archaeolipids of the TPL, which are recognized by a receptor specialized in uptake and not involved in downstream signaling. Despite dsLp alone was also immunostimulatory on J774A1 cells, applied twice a week on consecutive days along 7 weeks on Balb/c mice, it raised no measurable response unless associated to UDL or UDA. The highest systemic response, IgGa2 mediated, 1 log lower than im dsLp Al2O3, was elicited by dsLp-UDA. Such findings suggest that in vivo, UDL and UDA acted as penetration enhancers for dsLp, but only dsLp-UDA, owed to its pronounced uptake by APC, succeeded as topical adjuvants. The actual TPL composition, fully made of sn2,3 ether linked saturated archaeolipids, gives the UDA bilayer resistance against chemical, physical and enzymatic attacks that destroy ordinary phospholipids bilayers. Together, these properties make UDA a promising platform for topical drug targeted delivery and vaccination, that may be of help for countries with a deficient healthcare system.

show abstract

“…However, there are reasons for optimism that one or more safe and effective vaccines against leishmaniasis might be developed ( 3 , 5 , 6 ). A number of parasite antigens have been identified as candidates for vaccine development ( 5 ), including Leishmania analog receptor for activated C kinase (LACK) ( 7 ). Leishmania -activated C-kinase antigen (LACK) is a 36 kDa protein highly conserved across Leishmania species, and is expressed by both promastigotes and amastigotes ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…Leishmania -activated C-kinase antigen (LACK) is a 36 kDa protein highly conserved across Leishmania species, and is expressed by both promastigotes and amastigotes ( 8 ). LACK antigen from Leishmania braziliensis, Leishmania guyanensis , and Leishmania amazonensis induces the production of IFN-γ and IL-10 in peripheral blood mononuclear cells (PBMC) from patients with cutaneous leishmaniasis (CL), and IL-10 in those of naïve individuals ( 7 , 9 – 12 ). LACK drives the expansion of IL-4 secreting T cells ( 13 ), and for that reason LACK vaccination trials used approaches, like cytokines or DNA vectors, to redirect early IL-4 responses to a protective Th1 response ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Antigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters

et al. 2018

View full text Add to dashboard Cite

Leishmania-activated C-kinase antigen (LACK) is a highly conserved protein among Leishmania species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65) expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL). Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas. However, whether LACK is capable to trigger cytokine release by peripheral blood mononuclear cells from patients cured of CL due to Leishmania infantum (L. infantum) or induce protection in L. infantum-infected hamsters [visceral leishmaniasis (VL) model], has not yet been analyzed. The present work examines the ex vivo immunogenicity of LACK in cured VL and CL patients, and asymptomatic subjects from an L. infantum area. It also evaluates the vaccine potential of LACK against L. infantum infection in hamsters, in a protocol of priming with plasmid pCI-neo-LACK (DNA-LACK) followed by a booster with the poxvirus vectors MVA-LACK or M65-LACK. LACK-stimulated PBMC from both asymptomatic and cured subjects responded by producing IFN-γ, TNF-α, and granzyme B (Th1-type response). Further, 78% of PBMC samples that responded to soluble Leishmania antigen showed IFN-γ secretion following stimulation with LACK. In hamsters, the protocol of DNA-LACK prime/MVA-LACK or M65-LACK virus boost vaccination significantly reduced the amount of Leishmania DNA in the liver and bone marrow, with no differences recorded between the use of MVA or M65 virus vector options. In summary, the Th1-type and cytotoxic responses elicited by LACK in PBMC from human subjects infected with L. infantum, and the parasite protective effect of prime/boost vaccination in hamsters with DNA-LACK/MVA-LACK and DNA-LACK/M65-LACK, revealed the significance of LACK in activating human and hamster immune responses and support LACK to be a valuable candidate for inclusion in a vaccine against human VL.

show abstract

Contrasting human cytokine responses to promastigote whole-cell extract and the Leishmania analogue receptor for activated C kinase antigen of L. amazonensis in natural infection versus immunization

Cited by 12 publications

References 28 publications

Cellular and Humoral Responses toLeishmania majorVirulence Factors in Healed Cutaneous Leishmaniasis and Mediterranean Visceral Leishmaniasis Patients

Cellular and Humoral Responses toLeishmania majorVirulence Factors in Healed Cutaneous Leishmaniasis and Mediterranean Visceral Leishmaniasis Patients

Ultradeformable Archaeosomes for Needle Free Nanovaccination with Leishmania braziliensis Antigens

Antigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters

Contact Info

Product

Resources

About