scholarly journals Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis

npj Vaccines ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Elodie Petitdidier ◽  
Julie Pagniez ◽  
Joana Pissarra ◽  
Philippe Holzmuller ◽  
Gérard Papierok ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Parasite Burden ◽  
Control Group ◽  
Preclinical Trial ◽  
Ifn Γ ◽  
Secretory Products ◽  
Carboxy Terminal ◽  
Zoonotic Visceral Leishmaniasis

AbstractDogs are the main reservoir of zoonotic visceral leishmaniasis. Vaccination is a promising approach to help control leishmaniasis and to interrupt transmission of the Leishmania parasite. The promastigote surface antigen (PSA) is a highly immunogenic component of Leishmania excretory/secretory products. A vaccine based on three peptides derived from the carboxy-terminal part of Leishmania amazonensis PSA and conserved among Leishmania species, formulated with QA-21 as adjuvant, was tested on naive Beagle dogs in a preclinical trial. Four months after the full course of vaccination, dogs were experimentally infected with Leishmania infantum promastigotes. Immunization of dogs with peptide-based vaccine conferred immunity against experimental infection with L. infantum. Evidence for macrophage nitric oxide production and anti-leishmanial activity associated with IFN-γ production by lymphocytes was only found in the vaccinated group. An increase in specific IgG2 antibodies was also measured in vaccinated dogs from 2 months after immunization. Additionally, after challenge with L. infantum, the parasite burden was significantly lower in vaccinated dogs than in the control group. These data strongly suggest that this peptide-based vaccine candidate generated cross-protection against zoonotic leishmaniasis by inducing a Th1-type immune response associated with production of specific IgG2 antibodies. This preclinical trial including a peptide-based vaccine against leishmaniasis clearly demonstrates effective protection in a natural host. This approach deserves further investigation to enhance the immunogenicity of the peptides and to consider the possible engineering of a vaccine targeting several Leishmania species.

scholarly journals The Role of Interleukine-10 and Interferon-γ as Potential Markers of the Evolution of African Swine Fever Virus Infection in Wild Boar

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 757
Author(s):  
Sandra Barroso-Arévalo ◽  
Jose A. Barasona ◽  
Estefanía Cadenas-Fernández ◽  
José M. Sánchez-Vizcaíno
Keyword(s):  
Wild Boar ◽  
Vaccine Candidate ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Interferon Γ ◽  
Fever Virus ◽  
Control Group ◽  
Challenge Virus ◽  
Ifn Γ

African swine fever virus (ASFv) is one of the most challenging pathogens to affect both domestic and wild pigs. The disease has now spread to Europe and Asia, causing great damage to the pig industry. Although no commercial vaccine with which to control the disease is, as yet, available, some potential vaccine candidates have shown good results in terms of protection. However, little is known about the host immune mechanisms underlying that protection, especially in wild boar, which is the main reservoir of the disease in Europe. Here, we study the role played by two cytokines (IL-10 and IFN-γ) in wild boar orally inoculated with the attenuated vaccine candidate Lv17/WB/Rie1 and challenged with a virulent ASFv genotype II isolate. A group of naïve wild boar challenged with the latter isolate was also established as a control group. Our results showed that both cytokines play a key role in protecting the host against the challenge virus. While high levels of IL-10 in serum may trigger an immune system malfunctioning in challenged animals, the provision of stable levels of this cytokine over time may help to control the disease. This, together with high and timely induction of IFN-γ by the vaccine candidate, could help protect animals from fatal outcomes. Further studies should be conducted in order to support these preliminary results and confirm the role of these two cytokines as potential markers of the evolution of ASFV infection.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

scholarly journals Neutrophils, eosinophils, and mast cells in the intestinal wall of dogs naturally infected with Leishmania infantum

2018 ◽  
Vol 27 (4) ◽  
pp. 430-438 ◽  
Author(s):  
Diogo Tiago da Silva ◽  
Maria Luana Alves ◽  
Júlio Cesar Pereira Spada ◽  
Rita de Cássia Viveiros da Silveira ◽  
Trícia Maria Ferreira de Sousa Oliveira ◽  
...  
Keyword(s):  
Mast Cells ◽  
Visceral Leishmaniasis ◽  
Leishmania Infantum ◽  
Parasite Burden ◽  
Inverse Correlation ◽  
Muscle Layer ◽  
Intestinal Wall ◽  
Control Group ◽  
Cell Hyperplasia ◽  
Cell Counts

Abstract Visceral leishmaniasis (VL) is a disease caused by the protozoa Leishmania infantum and can cause an inflammatory reaction in the gastrointestinal tract, however the role of granulocytic cells (neutrophils, eosinophils, and mast cells) in the intestine of dogs infected is not fully understood. We performed a quantitative analysis these cells in the intestinal wall of dogs with canine visceral leishmaniasis (CVL). Twenty dogs were assigned to one of three groups: group 1 (G1, n=8), dogs with CVL and L. infantum amastigotes in the intestine; group 2 (G2, n=9), dogs with CVL but without intestinal amastigotes; and group 3 (G3, n=3), uninfected dogs (control group). Granulocytic cells were counted in the crypt-villus unit (mucosa), submucosa, and muscle layer of the intestinal mucosa. Cell counts were higher in the intestinal wall of dogs from G2 followed by G1 and G3 (p≤0.05). In G1, there was a low inverse correlation between parasite burden of the small intestine and granulocyte counts (r= -0.1, p≤0.01). However, in G2 dogs, mast cell and eosinophil numbers showed positive correlation (r=0.85, p≤0.01). The granulocytic cell hyperplasia observed in the intestine of L. infantum-infected dogs suggests that these cells may be involved in the cell-mediated immune response for parasite elimination.

Molecular, biochemical characterization and assessment of immunogenic potential of cofactor-independent phosphoglycerate mutase againstLeishmania donovani: a step towards exploring novel vaccine candidate

Parasitology ◽  
2017 ◽  
Vol 145 (4) ◽  
pp. 508-526 ◽  
Author(s):  
RATI TANDON ◽  
SHARAT CHANDRA ◽  
RAJENDRA KUMAR BAHARIA ◽  
PRAGYA MISRA ◽  
SANCHITA DAS ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Mrna Expression ◽  
T Helper Cells ◽  
Clinical Remission ◽  
Vaccine Candidate ◽  
No Production ◽  
T Helper ◽  
Prophylactic Efficacy ◽  
Helper Cells ◽  
Ifn Γ

SUMMARYDespite immense efforts, vaccine against visceral leishmaniasis has yet not been developed. Earlier our proteomic study revealed a novel protein, cofactor-independent phoshoglycerate mutase (LdiPGAM), an important enzyme in glucose metabolism, in T helper cells type 1 (Th1) stimulatory region of solubleLeishmania donovaniantigen. In this study, LdiPGAM was biochemically and molecularly characterized and evaluated for its immunogenicity and prophylactic efficacy againstL. donovani. Immunogenicity of recombinant LdiPGAM (rLdiPGAM) was initially assessed in naïve hamsters immunized with it by analysing mRNA expression of inducible nitric oxide (NO) synthase (iNOS) and other Th1/T helper cells type 2 cytokines, which revealed an upregulation of Th1 cytokines along with iNOS. Immunogenicity of rLdiPGAM was further evaluated in lymphocytes of treatedLeishmania-infected hamsters and peripheral blood mononuclear cells ofLeishmaniapatients in clinical remission by various parameters, viz. lymphoproliferation assay and NO production (hamsters and patients) and levels of various cytokines (patients). rLdiPGAM induced remarkable Lymphoproliferative response and NO production in treatedLeishmania-infected hamsters as well as in patients and increase in interferon gamma (IFN-γ), interleukin-12 (IL-12p40) responses inLeishmaniapatients in clinical remission. Vaccination with rLdiPGAM exerted considerable prophylactic efficacy (73%) supported by increase in mRNA expression of iNOS, IFN-γ and IL-12p40 with decrease in transforming growth factor beta and interleukin-10. Above results indicate the importance of rLdiPGAM protein as a potential vaccine candidate against visceral leishmaniasis.

scholarly journals Experimental visceral leishmaniasis in high and low antibody - producer mice (selection IV-A)

1999 ◽  
Vol 32 (3) ◽  
pp. 229-234 ◽  
Author(s):  
Cristiane Jellmayer Fechio ◽  
Angela Maria Victoriano de Campos Soares ◽  
Silvio Luís de Oliveira ◽  
Alexandrina Sartori
Keyword(s):  
Visceral Leishmaniasis ◽  
Protective Immunity ◽  
Macrophage Activation ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
Parasite Infection ◽  
High Antibody ◽  
Splenic Cells ◽  
Splenic Index ◽  
Direct Counts

Leishmaniasis is a typical parasite infection whose protective immunity depends on macrophage activation. Susceptibility to Leishmania donovani infection was compared in H (high antibody responder) and L (low antibody responder) mice from selection IV-A. H mice infected intravenously with 10(7) amastigotes of L. donovani were more susceptible to infection than their L counterparts. This higher susceptibility was characterized by a higher splenic and hepatic parasite burden. An increased splenic index was observed in both lines after sixty days of infection. This splenomegaly was caused, at least partially, by an increase in the number of splenic cells as determined by direct counts of cells from spleen. The results show that selection IV-A is susceptible to visceral leishmaniasis, with the H line being more susceptible than the L line.

scholarly journals Role of NK Cells and Gamma Interferon in Transplacental Passage of Toxoplasma gondii in a Mouse Model of Primary Infection

2004 ◽  
Vol 72 (3) ◽  
pp. 1397-1401 ◽  
Author(s):  
Ahmed Abou-Bacar ◽  
Alexander W. Pfaff ◽  
Sophie Georges ◽  
Valérie Letscher-Bru ◽  
Denis Filisetti ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Nk Cells ◽  
Protective Immunity ◽  
Nk Cell ◽  
Congenital Toxoplasmosis ◽  
Parasite Burden ◽  
Blood Parasite ◽  
Gamma Interferon ◽  
Recombination Activating Gene ◽  
Ifn Γ

ABSTRACT Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-γ). To clarify the roles of NK cells and IFN-γ in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2−/−) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2−/− mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-γ secretion by spleen cells, and decreased parasitemia. In the RAG-2−/− mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-γ in both infected RAG-2−/− and BALB/c mice decreased congenital Toxoplasma transmission, contrasting with an exacerbation of maternal infection. These data suggest that a partially protective immunity against congenital toxoplasmosis is achieved due to the increased number of NK cells in RAG-2−/− mice. However, it seems that IFN-γ enhances, directly or indirectly, the transplacental transmission.

scholarly journals Concomitant infection with Leishmania donovani and Plasmodium berghei alters clinical and immune responses in BALB/c mice

2021 ◽  
Author(s):  
Rebeccah Moraa Ayako ◽  
Joshua Muli Mutiso ◽  
John Chege Macharia ◽  
David Langoi ◽  
Lucy Ochola
Keyword(s):  
Body Weight ◽  
Visceral Leishmaniasis ◽  
Plasmodium Berghei ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
Parasite Load ◽  
Early Screening ◽  
Immunological Parameters ◽  
Geographical Regions ◽  
Ifn Γ

Malaria and visceral leishmaniasis coexist in the same geographical regions. However, dual co-infection with parasites causing these diseases and their impact on public health is poorly documented. Interactions between these parasites may play a role in disease outcome. The present study set out to evaluate the clinical and immunological parameters following Leishmania donovani and Plasmodium berghei co-infection in BALB/c mice. Mice were divided into four groups; L. donovani- only, L. donovani- P. berghei , P. berghei- only and naïve. Body weight, parasite burden, total IgG, IFN-γ and IL-4 responses were determined. To determine the survival rate, four mice were used from each group. Tissues for histological analysis were taken from spleen, liver and brain. Results indicated significant differences in body weight (P<0.0001), L. donovani parasite load (P< 0.0001 ), L. donovani IgG (P< 0.0001), P. berghei parasitemia (P= 0.0222), P. berghei IgG (P= 0.002), IFN-γ (P<0.0001) and IL-4 (P<0.0001) in dual-infected mice. There was no correlation between L. donovani parasite load and IgG responses in single or dual infections, while there was a positive relationship of P. berghei parasitemia and IgG responses in the dual infection group only. Plasmodium berghei had the highest mortality rate compared to L. donovani - only and L. donovani- P. berghei infected mice groups. Histological analyses showed enlarged red and white pulps and pathological changes in the spleen, liver and brain tissues which were less pronounced in co-infected group. We conclude that L. donovani and P. berghei co-infection reduces disease severity and these changes seem to correlate with variation in serum IgG and cytokines (IFN-γ and IL-4). Therefore, the study recommends the importance of inclusion of early screening of malaria in Visceral Leishmaniasis patients in regions where malaria is co- endemic.

scholarly journals Immunogenicity and potential protection of DNA vaccine of Leishmania martiniquensis against Leishmania infection in mice

2021 ◽  
Vol 15 (09) ◽  
pp. 1328-1338
Author(s):  
Thuntawat Aunguldee ◽  
Orapin Gerdprasert ◽  
Piyatida Tangteerawatana ◽  
Amporn Jariyapongskul ◽  
Saovanee Leelayoova ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Consensus Sequence ◽  
Parasite Burden ◽  
Interleukin 10 ◽  
Leishmania Infection ◽  
Control Group ◽  
Ifn Γ ◽  
Polymerase Chain ◽  
Immunocompromised Hosts ◽  
Partial Consensus

Introduction: In Thailand, Leishmania martiniquensis is the predominant species causing cutaneous and visceral leishmaniasis. Its incidence has been increasing among immunocompetent and immunocompromised hosts. We developed a prototype DNA vaccine using a partial consensus sequence of the cysteine protease B (cpb) gene derived from L. martiniquensis from Thai patients. Methodology: The laboratory inbred strain of albino BALB/c mice were immunized intramuscularly three times at 2-week intervals (weeks 0, 2, and 4) with cpb plasmid DNA (pcDNA_cpb) with or without the adjuvant, monoolein (pcDNA_cpb-MO). Mice were challenged at week 6 with L. martiniquensis promastigotes. Sera were analysed for IgG1, IgG2a, interferon gamma and interleukin 10 (IFN-γ and IL-10, respectively) levels at weeks 0, 4, and 9. Additionally, livers and spleens were also analysed for parasite burden using immunohistochemistry and real-time polymerase chain (qPCR) assays. Results: Three weeks after promastigote challenge, vaccinated mice showed significantly increased levels of IgG2a and IFN-γ while IL-10 level was significantly reduced when compared with those in the control group (p < 0.01). Parasite burden in the livers and spleens of vaccinated mice significantly decreased. In addition, a significant increase in mature granuloma formation in the livers when compared with those of the control group (p < 0.05) was found, indicating increased T-helper cells (Th1)-induced inflammation and destruction of amastigotes. Monoolein produced a booster effect to enhance the mouse Th1 protective immunity. Conclusions: The prototype DNA vaccine could induce a Th1 immune response that conferred potential protection to the L. martiniquensis promastigote challenge in BALB/c mice.

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