scholarly journals BALB/c Mice Vaccinated withLeishmania majorRibosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Laura Ramírez ◽  
Salvador Iborra ◽  
Jimena Cortés ◽  
Pedro Bonay ◽  
Carlos Alonso ◽  
...  

Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primaryLeishmania majorinfection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondaryLeishmania majorchallenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γin the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmaniaantibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity.

2018 ◽  
Author(s):  
Franciele Carolina Silva ◽  
Vinicius Dantas Martins ◽  
Felipe Caixeta ◽  
Matheus Batista Carneiro ◽  
Graziele Ribeiro Goes ◽  
...  

AbstractAn association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production by draining lymph node cells between control and obese mice, but obese mice presented higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal macrophages was found when these cells were obtained from obese mice when compared to lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from control mice to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice without affecting the development of Th1 response.Author SummaryThe obesity is a public health problem and it is reaching extraordinary numbers in the world and others diseases are being involved and aggravated as consequence of obesity. What we know is that some diseases are more severe in obese people than in normal people. We did not know how obesity changes the profile of immune response to infectious agents, leading to the more severe diseases. That‘s why we decided to investigate how obese mice lead with Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from obese mice and stimulated the cells with IL-17, and we observed that the macrophages from obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our results suggest that diet induced obesity decrease the resistance to infection.


2002 ◽  
Vol 195 (12) ◽  
pp. 1565-1573 ◽  
Author(s):  
Elizabeth G. Rhee ◽  
Susana Mendez ◽  
Javeed A. Shah ◽  
Chang-you Wu ◽  
Joanna R. Kirman ◽  
...  

CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive cellular immune responses. In this report, the ability of CpG ODN to confer long-term immunity and protection when used as a vaccine adjuvant with a clinical grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant leishmanial protein was studied. In two different mouse models of L. major infection, vaccination with ALM plus CpG ODN was able to control infection and markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6 (B6) mice, respectively, up to 12 wk after immunization. Moreover, B6 mice immunized with ALM plus CpG ODNs were still protected against infectious challenge even 6 mo after vaccination. In terms of immune correlates of protection, ALM plus CpG ODN-vaccinated mice displayed L. major–specific T helper cell 1 and CD8+ responses. In addition, complete protection was markedly abrogated in mice depleted of CD8+ T cells at the time of vaccination. Similarly, mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long-term protection that was dependent on CD8+ T cells in vivo. Together, these data demonstrate that CpG ODN, when used as a vaccine adjuvant with either a recombinant protein or heat-killed leishmanial antigen, can induce long-term protection against an intracellular infection in a CD8-dependent manner.


2018 ◽  
Vol 17 (2) ◽  
pp. 83-89 ◽  
Author(s):  
I. Zeouk ◽  
A. Et-Touys ◽  
M. Balouiri ◽  
H. Fellah ◽  
A. El Ouali Lalami ◽  
...  

According to the World Health Organization, leishmaniasis remains a major worldwide public health problem. The province of Sefrou located in the center of Morocco is a focus of cutaneous leishmaniasis. The present study aims at evaluating the antileishmanial potential of Berberis sp.,Crataegus oxyacantha, Cistus salviifolius, Ephedra altissima and Lavandula dentatafrequently used by the local population. Methanolic extracts were tested against the promastigote form ofLeishmania tropica, Leishmania majorandLeishmania infantumusing tetrazolium-based colorimetric (MTT) assay. The total phenol and flavonoids content of all extracts were determined using the Folin–Ciocalteu reagent, aluminum chloride, and potassium acetate solutions respectively. The plant extracts exhibited antileishmanial activity with variability depending on the tested strain and the plant species compared to Glucantime® used as control (IC50 (the half maximal inhibitory concentration) > 1,000 μg/mL). The best inhibition was observed with Berberis sp., againstLeishmania major(IC50 = 394.40 ± 3.02 μg/ml), andEphedra altissima(reported for the first time) againstLeishmania infantum(IC50 = 490.84 ± 3.15 μg/mL).Leishmania tropicahas shown the same sensitivity behavior toward the five extracts (in average IC50 = 540 ± 11.20 μg/mL). The total phenolic content was higher forCrataegus oxyacanthaandCistus salviifolius(140.67 ± 3.17 μg eq Gallic Acid (GA)/ mg of Extract (E) and 133.83 ± 9.03 μg eq GA/mg of E respectively), while flavonoid was higher forCistus salviifoliusandLavandula dentata(57.92 ± 2.46 μg eq Quercetin (Que)/ mg of Extract (E) and 41.53 ± 1.74 μg eq Que/mg of E). All the tested extracts present some promising aspects that may cure cutaneous leishmaniasis in the center of Morocco; further bioguided assays are needed to isolate the fractions and the bioactive molecule.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
D Panatto ◽  
P Landa ◽  
D Amicizia ◽  
P L Lai ◽  
E Lecini ◽  
...  

Abstract Background Invasive disease due to Neisseria meningitidis (Nm) is a serious public health problem even in developed countries, owing to its high lethality rate (8-15%) and the invalidating sequelae suffered by many (up to 60%) survivors. As the microorganism is transmitted via the airborne route, the only available weapon in the fight against Nm invasive disease is vaccination. Our aim was to carry out an HTA to evaluate the costs and benefits of anti-meningococcal B (MenB) vaccination with Trumenba® in adolescents in Italy, while also considering the impact of this new vaccination strategy on organizational and ethics aspects. Methods A lifetime Markov model was developed. MenB vaccination with the two-dose schedule of Trumenba® in adolescents was compared with 'non-vaccination'. Two perspectives were considered: the National Health Service (NHS) and society. Three disease phases were defined: acute, post-acute and long-term. Epidemiological, economic and health utilities data were taken from Italian and international literature. The analysis was conducted by means of Microsoft Excel 2010®. Results Our study indicated that vaccinating adolescents (11th year of life) with Trumenba® was cost-effective with an ICER = € 7,912/QALY from the NHS perspective and € 7,758/QALY from the perspective of society. Vaccinating adolescents reduces the number of cases of disease due to meningococcus B in one of the periods of highest incidence of the disease, resulting in significant economic and health savings. Conclusions This is the first study to evaluate the overall impact of free MenB vaccination in adolescents both in Italy and in the international setting. Although cases of invasive disease due to meningococcus B are few, if the overall impact of the disease is adequately considered, it becomes clear that including anti-meningococcal B vaccination into the immunization program for adolescents is strongly recommended from the health and economic standpoints. Key messages Free, large-scale MenB vaccination is key to strengthening the global fight against invasive meningococcal disease. Anti-meningococcal B vaccination in adolescents is a cost-effective health opportunity.


2021 ◽  
Vol 22 (4) ◽  
pp. 1883
Author(s):  
Coralia Cotoraci ◽  
Alina Ciceu ◽  
Alciona Sasu ◽  
Anca Hermenean

Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.


2021 ◽  
Vol 22 (2) ◽  
pp. 599
Author(s):  
Lucia Carboni ◽  
Luisa Ponzoni ◽  
Daniela Braida ◽  
Mariaelvina Sala ◽  
Cecilia Gotti ◽  
...  

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.


2003 ◽  
Vol 71 (11) ◽  
pp. 6562-6572 ◽  
Author(s):  
Salvador Iborra ◽  
Manuel Soto ◽  
Javier Carrión ◽  
Ana Nieto ◽  
Edgar Fernández ◽  
...  

ABSTRACT In this study, we examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0), were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like humoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-γ) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection against L. major infection was achieved, as determined by both lesion development and parasite burden. Immunization of mice with LiP0-DNA primes both CD4+ and CD8+ T cells, which, with the L. major challenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-γ. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.


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