Nucleoside Hydrolase (NH36) Domains Induce T-Cell Cytokine Responses in Human Visceral Leishmaniasis.

Development of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains.

A Chimera Containing CD4+ and CD8+ T-Cell Epitopes of the Nucleoside Hydrolase (NH36) Optimizes Cross-Protection against Infection.

The nucleoside hydrolase (NH36) and NH A34480 of share 93% of sequence identity. In mice, the NH36 induced protection against visceral leishmaniasis is mediated by a CD4+ T cell response against its C-terminal domain (F3). Besides this CD4+ Th1 response, prevention and cure of infection require also additional CD8+ and regulatory T-cell responses to the NH36 N-terminal (F1 domain).

Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection.

Nucleoside hydrolases of the Leishmania genus are vital enzymes for the replication of the DNA and conserved phylogenetic markers of the parasites. Leishmania donovani nucleoside hydrolase (NH36) induced a main CD4(+) T cell driven protective response against L. chagasi infection in mice which is directed against its C-terminal domain.

Cross-Protective Immunity to Leishmania amazonensis is Mediated by CD4+ and CD8+ Epitopes of Leishmania donovani Nucleoside Hydrolase Terminal Domains.

The nucleoside hydrolase (NH) of Leishmania donovani (NH36) is a phylogenetic marker of high homology among Leishmania parasites. In mice and dog vaccination, NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3). The C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis.

Resistance to visceral leishmaniasis is severely compromised in mice deficient of bradykinin B2-receptors.

Background: Kinins liberated from plasma-borne kininogens, are potent innate stimulatory signals. We evaluated whether resistance to infection by Leishmania (L.) chagasi depends on activation of G-protein coupled bradykinin B2 receptors (B2R).

The adjuvanticity of Chiococca alba saponins increases with the length and hydrophilicity of their sugar chains.

The saponins of Chiococca alba are triterpene bidesmosides that contain glycidic moieties attached to the C-3 and C-28 carbon of their aglycone. We describe that their adjuvant potential increases in direct relationship to the length and hydrophilicity of the C-28 attached sugar chain which contains: arabinose-rhamnose in the CA2, arabinose-rhamnose-xylose in the CA3X; arabinose-rhamnose-apiose in the CA3 and arabinose-rhamnose-apiose-apiose in the CA4 saponin. The hydrophile/lipophile balance calculated for CA2 was 12.

Adaptive immunity against Leishmania nucleoside hydrolase maps its c-terminal domain as the target of the CD4+ T cell-driven protective response.

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens.

Decrease of the incidence of human and canine visceral leishmaniasis after dog vaccination with Leishmune in Brazilian endemic areas.

Leishmune, the first prophylactic vaccine licensed against canine visceral leishmaniasis (CVL), has been used in Brazil since 2004, where seropositive dogs are sacrificed in order to control human visceral leishmaniasis (VL). We demonstrate here that vaccination with Leishmune does not interfere with the serological control campaign (110,000 dogs). Only 1.

The mutation G298A-->Ala100Thr on the coding sequence of the Duffy antigen/chemokine receptor gene in non-caucasian Brazilians.

Ala100Thr has been suggested to be a Caucasian genetic marker on the FY*B allele. As the Brazilian population has arisen from miscegenation among Portuguese, Africans, and Indians, this mutation could possibly be found in Euro- and Afro-Brazilians, or in Brazilian Indians. Fifty-three related individuals and a random sample of 100 subjects from the Brazilian population were investigated using the polymerase chain reaction and four restriction fragment length polymorphisms.

Pulcherrimasaponin, from the leaves of Calliandra pulcherrima, as adjuvant for immunization in the murine model of visceral leishmaniasis.

A novel triterpenoidal saponin, called pulcherrimasaponin (CP05), isolated from the leaves of Calliandra pulcherrima Benth. shows remarkable similarities to the previously described potent adjuvant, QS21 saponin (Quillaja saponaria Molina). On the basis of chemical and physicochemical evidence, its structure was established as [3beta,16alpha,28[2E,6S[2E,6S(2E,6S)]]]-olean-12-en-28-oic acid 3-[[O-alpha-l-arabinopyranosyl-(1-->2)-O-alpha-l-arabinopyranosyl-(1-->6)-2-(acetylamino)-2-deoxy-beta-d-glucopyranosyl]oxy]-16-hydroxy-O-beta-d-glucopyranosyl-(1-->3)-O-[O-beta-d-xylopyranosyl-(1-->3)-beta-d-xylopyranosyl-(1-->4)-O-6-deoxy-alpha-l-mannopyranosyl-(1-->2)-6-O-[6-[[2-O-2,6-dimethyl-1-oxo-6-(beta-d-xylopyranosyloxy)-2,7-octadienyl]-[(6-deoxy-beta-d-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-beta-d-xylopyranosyl]oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-beta-d-glucopyranosyl ester.

Improving methods for epidemiological control of canine visceral leishmaniasis based on a mathematical model. Impact on the incidence of the canine and human disease.

The mathematical model described by Dye (1996) condemned the epidemiological canine visceral leishmaniasis control campaign, considering it non-efficient. Using this model, we mathematically demonstrate that the control is not efficient, only at low kappa values (rate at which latent and infectious dogs are lost by the destruction program) which match the canine seropositivity observed in the field by the immunofluorescency (IF) blood eluates analysis. With higher k values, corresponding to IF (kappa = 0.

Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine.

The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection.

Immunotherapy against murine experimental visceral leishmaniasis with the FML-vaccine.

The fucose mannose ligand (Leishmania donovani FML)-saponin vaccine has earlier shown its immunoprophylactic potential against visceral leishmaniasis in the CB hamster (87.7% of parasite load reduction), Balb/c (84.4%) and Swiss albino mouse (85-93%) models.

IgG1/IgG2 antibody dichotomy in sera of vaccinated or naturally infected dogs with visceral leishmaniosis.

Canine antibody IgG, IgG1 and IgG2 anti-FML responses were investigated in dogs vaccinated with the fucose-mannose ligand (FML)-vaccine of Leishmania donovani and in dogs with naturally acquired visceral leishmaniosis. While similar levels of total IgG antibodies were seen in the seropositive naturally infected dogs and in vaccinees, significant differences between the groups were found regarding their IgG1/IgG2 anti-FML antibody composition (P<0.005).

Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis.

The FML antigen of Leishmania donovani, in combination with either Riedel de Haën (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12.

Ethnicity and type 2 diabetes in Rio de Janeiro, Brazil, with a review of the prevalence of the disease in Amerindians.

To what extent can ethnic factors contribute to the prevalence of type 2 diabetes and impaired glucose tolerance (IGT) in an urban Brazilian population? Conversely, how can environmental factors such as diet change these prevalences in a given ethnic group, in this case Brazilian Indians? To answer these questions estimates of ethnic admixture in Afro- and Euro-Brazilians from Rio de Janeiro, Brazil, were established using eight genetic systems and compared with the prevalences of these conditions obtained previously. This information was integrated with results obtained inside and outside of Brazil. The similarity of prevalences for type 2 diabetes and IGT in Afro- and Euro-Brazilians may be related to the extensive gene flow that occurred between them and to similar socioeconomic levels in the samples investigated.

Analysis of the -1185A/G von Willebrand factor (VWF) gene polymorphism in two Brazilian ethnic groups and its effect on the plasma VWF levels.

Both genetic and environmental factors influence the variation in von Willebrand factor (VWF) levels between individuals, the main genetic variable known to be involved in differences in VWF levels being the ABO blood group. The -1185A/G polymorphism in the 5'-regulatory region of VWF gene has been associated with plasma VWF levels in a normal population. The objective of our study was to examine the relationship between the -1185A/G polymorphism and plasma VWF levels in a total of 420 individuals from two Brazilian ethnic groups.