scholarly journals Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 352
Author(s):  
Abel Martínez-Rodrigo ◽  
Alicia Mas ◽  
Daniel Álvarez-Campos ◽  
José A. Orden ◽  
Gustavo Domínguez-Bernal ◽  
...  

Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

2018 ◽  
Vol 6 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Fatemeh Tabatabaie ◽  
Nasim Samarghandi ◽  
Somayeh Zarrati ◽  
Fatemeh Maleki ◽  
Mehdi Shafiee Ardestani ◽  
...  

BACKGROUND: Leishmaniasis is a parasitic disease induced by a protozoan from the genus Leishmania. No effective vaccine has yet been developed against the disease.AIM: In this work, two nano-vaccines, TSA recombinant plasmid and dendrimer and poly (methyl methacrylate) (PMMA) nanoparticles (as adjuvants), were designed and tested for their immunogenicity in BALB/c mice.METHODS: After the plasmid construction and preparation of adjuvants, three intramuscular injections of the nano-vaccines (100 µg) and the recombinant TSA protein (20 µg) were subcutaneously performed. Eventually, the challenged animals were infected with the parasites (1*106 promastigotes). After the last injections of the nano-vaccines, the responses of their antibody subclasses and cytokines were assessed via ELISA method before and after the challenge.RESULTS: This study revealed that the new nano-vaccines were strong and effective in inducing specific antibody and cellular responses and reducing the parasite burden in the spleen compared to the control groups of Leishmania major-infected BALB/c mice.CONCLUSION: Based on the results, we can suggest that the formulated vaccines are suitable candidates for further studies in the field of leishmaniasis control. 


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


1975 ◽  
Vol 34 (02) ◽  
pp. 498-503 ◽  
Author(s):  
D Nyman ◽  
M. A da Silva ◽  
L. K Widmer ◽  
F Duckert

SummaryBrinase was administered intra-arterially in 16 patients with thrombotic or embolic arterial occlusions. Angiography could be performed before and after treatment in 13 patients. Thrombolysis was obtained in 3 of 9 patients with thrombotic and in 3 of 4 patients with embolic occlusions. In 3 patients severe local side effects occurred.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaotang Du ◽  
Jingjiao Wu ◽  
Meijuan Zhang ◽  
Yanan Gao ◽  
Donghui Zhang ◽  
...  

It is well accepted that IFN-γis important to the development of acquired resistance against murine schistosomiasis. However, thein vivorole of this immunoregulatory cytokine in helminth infection needs to be further investigated. In this study, parasite burden and host immune response were observed in IFN-γknockout mice (IFNg KO) infected withSchistosoma japonicumfor 6 weeks. The results suggested that deficiency in IFN-γled to decreased egg burden in mice, with low schistosome-specific IgG antibody response and enhanced activation of T cells during acute infection. Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. Furthermore, CD8+cells instead of NK cells of IFNg KO mice exhibited increased transcription of cytotoxic genes compared with WT mice. Additionally,Schistosoma japonicum-specific egg antigen immunization also could activate CD8+T cells to upregulate the expression of cytotoxic genes in IFNg KO mice. Our data suggest that IFN-γis not always a positive regulator of immune responses. In certain situations, the disruption of IFN-γsignaling may up-regulate the cytotoxic T-cell-mediated immune responses to the parasite.


Author(s):  
Mounir M El-safty ◽  
Hala Mahmoud ◽  
Eman Sa Zaki ◽  
Howaida I Abd-alla

  Objective: Salmonella enteritidis ghosts (SEGs) is a non-living empty bacterial cell envelopes which were generated using a different concentration of sodium hydroxide (NaOH) 6.4 mg/mL and evaluated as a vaccine candidate in specific pathogen-free (SPF) chicken. SEGs have been produced by chemical-mediated lysis and evaluated the potential efficacy of chemically induced SEG vaccine and its ability to induce protective immune responses against virulent S. enteritidis challenge in SPF chickens.Methods: SPF chickens were divided into three groups: Group A (non-vaccinated control), Group B (vaccinated with prepared vaccine), and Group C (vaccinated with commercial vaccine).Results: Vaccination of SPF chicken with SEGs induced higher immune responses before and after virulent challenge. SPF chicken vaccinated with SEGs showed increasing in serum enzyme-linked immunosorbent assay (ELISA) antibodies. During the vaccination period, Groups B and C showed higher serum antibody titer compared to Group A. The minimal inhibitory concentration (MIC) of NaOH was capable of inducing non-living SEGs, and it has successfully generated non-living SEGs by MIC of NaOH.Conclusion: It is a one-step process which means easy manufacturing and low production cost compared to protein E-mediated lysis method. Chemically induced SEG vaccine is a highly effective method for inducing protective immunity. This study strongly suggests that SEGs will be a permissive vaccine, as the method of inhibition of S. enteritidis was safe and cheaper than other methods, and it gave a good protection.


2004 ◽  
Vol 26 (1) ◽  
pp. 61 ◽  
Author(s):  
DW Cooper

Immunocontraception involves eliciting an immune response against eggs, sperm or hormones so that successful reproduction is prevented. Work in Australasia is aimed at European rabbits (Oryctolagus cuniculus), red foxes (Vulpes vulpes), house mice (Mus musculus), common brushtail possums (Trichosurus vulpecula), koalas (Phascolartcos cinereus) and kangaroos (Macropus spp.), with the vaccines involved all containing self antigens or their relatives. Two fundamental problems have been inadequately addressed in this research. The first problem is that it is difficult to obtain strong immune responses against self antigens and so the vaccines may be ineffective. Most published data on the effect of immunocontraceptives on reproduction involve the use of an adjuvant of which there are many kinds. The materials enhance the immune response greatly. The most frequently used is Freund?s adjuvant which can cause chronic suffering. Its use on wildlife will lead to very negative public perceptions. There has been no convincing demonstration that successful immunocontraception is possible with any method of vaccination likely to be used in the field, if success is defined as contraception of a proportion of the population high enough for management requirements. If it is assumed that success can be achieved, the second fundamental problem arises with two potential consequences. Even with adjuvant, a substantial minority of the vaccinated animals remains fertile. The first consequence is that since failure to be contracepted is likely to be in part genetic, there is likely to be rapid selection for these non-responders. The method will become ineffective in a few generations. The second problem is that the offspring of the animals which breed will have altered immune responses. Their capacities to respond to their own pathogens or to harbor pathogens of other species in the same ecosystem are likely to be changed. The presence of chlamydia in P. cinereus and bovine tuberculosis in New Zealand T. vulpecula means that responses to these pathogens would have to be studied in offspring of immunocontracepted parents to ensure that the offspring were not more susceptible to them. New Zealand intentions to put an immunocontraceptive into a T. vulpecula gut worm must be viewed with caution by Australia. The eggs of transgenic worms will be easily transplanted either accidentally or deliberately back into Australia, and so infect T. vulpecula in Australia.


2021 ◽  
Author(s):  
Christopher M Weiss ◽  
Hongwei Liu ◽  
Erin E Ball ◽  
Samuel Lam ◽  
Tomas Hode ◽  
...  

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in more than 4 million deaths in the 20 months since the virus was discovered. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout and vaccine hesitancy. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N-dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β-0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans. We tested GC as a potential countermeasure for COVID-19. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway and lungs. Our findings demonstrate a new application for soluble immunoadjuvants like GC for preventing severe disease associated with SARS-CoV-2.


2005 ◽  
Vol 2005 ◽  
pp. 17-17
Author(s):  
M. Clapperton ◽  
S. C. Bishop ◽  
N. D. Cameron ◽  
E. J. Glass

Productivity in pigs can be improved by continued selection, however the impact of such selection on immune responses and resistance towards infectious challenges is not known. A risk is that this method may lead to a correlated reduction in the immune response and disease resistance. To estimate the effect of selection for performance traits upon immune responses, we compared levels of immune traits between divergent lines of Large White pigs selected for either lean growth under restricted feeding or feed intake.


2019 ◽  
Vol 202 (9) ◽  
pp. 2558-2569 ◽  
Author(s):  
Shu-Chen Hung ◽  
Tieying Hou ◽  
Wei Jiang ◽  
Nan Wang ◽  
Shuo-Wang Qiao ◽  
...  

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 350 ◽  
Author(s):  
Maria Agallou ◽  
Maritsa Margaroni ◽  
Stathis D. Kotsakis ◽  
Evdokia Karagouni

Leishmaniases are complex vector-borne diseases caused by intracellular parasites of the genus Leishmania. The visceral form of the disease affects both humans and canids in tropical, subtropical, and Mediterranean regions. One health approach has suggested that controlling zoonotic visceral leishmaniasis (ZVL) could have an impact on the reduction of the human incidence of visceral leishmaniasis (VL). Despite the fact that a preventive vaccination could help with leishmaniasis elimination, effective vaccines that are able to elicit protective immune responses are currently lacking. In the present study, we designed a chimeric multi-epitope protein composed of multiple CD8+ and CD4+ T cell epitopes which were obtained from six highly immunogenic proteins previously identified by an immunoproteomics approach, and the N-termini of the heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis served as an adjuvant. A preclinical evaluation of the candidate vaccine in BALB/c mice showed that when it was given along with the adjuvant Addavax it was able to induce strong immune responses. Cellular responses were dominated by the presence of central and effector multifunctional CD4+ and CD8+ T memory cells. Importantly, the vaccination reduced the parasite burden in both short-term and long-term vaccinated mice challenged with Leishmania infantum. Protection was characterized by the continuing presence of IFN-γ+TNFα+-producing CD8+ and CD4+ T cells and increased NO levels. The depletion of CD8+ T cells in short-term vaccinated mice conferred a significant loss of protection in both target organs of the parasite, indicating a significant involvement of this population in the protection against L. infantum challenge. Thus, the overall data could be considered to be a proof-of-concept that the design of efficacious T cell vaccines with the help of reverse vaccinology approaches is possible.


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